Mouse Timeline Detailed: Difference between revisions
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{{Header}} | |||
== Introduction == | == Introduction == | ||
[[File:Mouse.jpg|left]] | [[File:Mouse.jpg|left]] | ||
This page is organised to show a detailed day by day development of sytems and features with approximate timing of key events. The staging by "days" relate to in the female presence of a vaginal plug indicating that the mating occurred, see [[Mouse_Timeline_Detailed#Timed_Pregnancy|timed pregnancy]]. | This {{mouse}} page is organised to show a detailed day by day development of sytems and features with approximate timing of key events. The staging by "days" relate to in the female presence of a vaginal plug indicating that the mating occurred, see [[Mouse_Timeline_Detailed#Timed_Pregnancy|timed pregnancy]]. | ||
'''Theiler Stages''' divides mouse development into 26 prenatal and 2 postnatal stages. <ref name="The House Mouse"> | '''Theiler Stages''' divides mouse development into 26 prenatal and 2 postnatal stages.<ref name="The House Mouse">{{Ref-Theiler1972}}</ref> | ||
'''Downs and Davies Stages''' is a more recent (1993) staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope. | '''Downs and Davies Stages''' is a more recent (1993) staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope.{{#pmid:8269852|PMID8269852}} | ||
There have been early online atlas{{#pmid:9007211|PMID9007211}} and several new staging papers and online atlases released.{{#pmid:26487781|PMID26487781}}{{#pmid:28185240|PMID28185240}} | |||
{{Mouse links}} | |||
{{Mouse E days}} | |||
== Week 1 == | == Week 1 == | ||
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[[File:Fertilization 001 icon.jpg|150px|link=Movie_-_Fertilization 01]] | [[File:Fertilization 001 icon.jpg|150px|link=Movie_-_Fertilization 01]] | ||
[[Movie_-_Fertilization 01|Fertilization | [[Movie_-_Fertilization 01|Fertilization]] | ||
Theiler Stage 2 - Dividing egg stage 2-4 cells. Zona pellucida present. First cleavage occurs at about 24 hours. Embryonic age = 1 dpc (range 1-2.5 dpc) | Theiler Stage 2 - Dividing egg stage 2-4 cells. Zona pellucida present. First cleavage occurs at about 24 hours. Embryonic age = 1 dpc (range 1-2.5 dpc) | ||
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Theiler Stage 6 - Attachment of blastocyst. Blastocyst implants, first evidence of embryonic endoderm cells covering the blastocoelic surface of the inner cell mass. Embryonic age = 4.5 dpc (range 4-5.5 dpc) | Theiler Stage 6 - Attachment of blastocyst. Blastocyst implants, first evidence of embryonic endoderm cells covering the blastocoelic surface of the inner cell mass. Embryonic age = 4.5 dpc (range 4-5.5 dpc) | ||
[[File:Mouse-early blastocyst 02.jpg|150px|Mouse hatched blastocyst]] | [[File:Mouse-hatching blastocyst.jpg|150px|Mouse hatching blastocyst]] [[File:Mouse-early blastocyst 02.jpg|150px|Mouse hatched blastocyst]] | ||
===Day 5 (E5.0)=== | ===Day 5 (E5.0)=== | ||
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Differentiation of egg cylinder. Implantation site 2x3mm.The maternal tissue is invaded by trophoblast (primary) giant cells and the ectoplacental cone is invaded by maternal blood. Differentiation of the egg cylinder into embryonic and extra-embryonic regions and the formation of the pro-amniotic cavity. Reichert's membrane, which is non-cellular and secreted by the distal endoderm, first appears. Embryonic age = 6 dpc (range 5-6.5 dpc) | Differentiation of egg cylinder. Implantation site 2x3mm.The maternal tissue is invaded by trophoblast (primary) giant cells and the ectoplacental cone is invaded by maternal blood. Differentiation of the egg cylinder into embryonic and extra-embryonic regions and the formation of the pro-amniotic cavity. Reichert's membrane, which is non-cellular and secreted by the distal endoderm, first appears. Embryonic age = 6 dpc (range 5-6.5 dpc) | ||
Theiler Stage 8 | ===Day 5 (E5.5)=== | ||
E5.5 Nodal signaling from the epiblast induces distal visceral endoderm (DVE) formation that will establish embryo anterior–posterior axis.{{#pmid:15302604|PMID15302604}} | |||
Theiler Stage 8 | |||
===Day 6 (E6.0)=== | ===Day 6 (E6.0)=== | ||
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'''Stage 9a '''Advanced Endometrial Reaction. Advanced egg-cylinder stage with the first evidence of an embryonic axis. Clear morphological distinction between the embryonic and extra-embryonic ectoderm. The ectoplacental cone is further invaded by maternal blood and the original lumen of the uterine crypt has disappeared. Equivalent Downs and Davies Stage : PS (pre-streak) | '''Stage 9a '''Advanced Endometrial Reaction. Advanced egg-cylinder stage with the first evidence of an embryonic axis. Clear morphological distinction between the embryonic and extra-embryonic ectoderm. The ectoplacental cone is further invaded by maternal blood and the original lumen of the uterine crypt has disappeared. Equivalent Downs and Davies Stage : PS (pre-streak) | ||
'''Stage 9b '''Advanced Endometrial Reaction. Late in this stage gastrulation begins, producing the first mesodermal cells. Equivalent Downs and Davies Stage : ES (early streak) | '''Stage 9b '''Advanced Endometrial Reaction. Late in this stage gastrulation begins, producing the first mesodermal cells. Equivalent Downs and Davies Stage : ES (early streak) | ||
===Day 6.5 (E6.5)=== | |||
* '''Heart''' - earliest heart precursors are 50 founder cells located on both sides of the midline in the epiblast of early gastrula stage embryos <ref><pubmed>9165112</pubmed></ref> | |||
===Day 7 (E7.0)=== | ===Day 7 (E7.0)=== | ||
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'''Stage 10c . '''Amnion. The allantoic bud first appears, gastrulation continues and the node becomes visible. Embryonic age = 7.0 dpc (range 6.5-7.5 dpc) (Equivalent Downs and Davies stages: MS - LS, mid-streak to late streak) | '''Stage 10c . '''Amnion. The allantoic bud first appears, gastrulation continues and the node becomes visible. Embryonic age = 7.0 dpc (range 6.5-7.5 dpc) (Equivalent Downs and Davies stages: MS - LS, mid-streak to late streak) | ||
===Day 7 (E7.5)=== | |||
{| | |||
| [[File:Mouse-_E7.5_early_bud.jpg|200px]] | |||
| [[File:Mouse-_E7.5_late_bud.jpg|100px]] | |||
|- | |||
| E7.5 early bud{{#pmid:19997484|PMID19997484}} | |||
| E7.5 late bud<ref name="PMID19997484" /> | |||
|} | |||
Theiler Stage 11 | Theiler Stage 11 | ||
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'''Stage11d '''Neural Plate, Presomite stage. Head folds continue to enlarge and the foregut pocket begins to form. Embryonic age = 7.5 dpc (range 7.25-8 dpc) ; LB-EHF-LHF (late allantoic bud to early head fold to late head fold) . Equivalent Downs & Davies stages: OB-EB (no allantoic bud to early allantoic bud) | '''Stage11d '''Neural Plate, Presomite stage. Head folds continue to enlarge and the foregut pocket begins to form. Embryonic age = 7.5 dpc (range 7.25-8 dpc) ; LB-EHF-LHF (late allantoic bud to early head fold to late head fold) . Equivalent Downs & Davies stages: OB-EB (no allantoic bud to early allantoic bud) | ||
* '''{{heart}}''' - migration of anterior lateral plate mesoderm towards midline, forms a linear heart tube.{{#pmid:16304598|PMID16304598}} | |||
== Week 2 == | == Week 2 == | ||
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'''Theiler Stage 13 - '''Turning of the embryo. This is a short period with turning initiated in embryos with 6-8 pairs of somites and usually completed in embryos with 14-16 pairs of somites. The first branchial arch has maxillary and mandibular components but the maxillary process is not visible until later (TS16). A second branchial arch is now evident. There is evidence of regionalisation of the heart and the neural tube is closed from a point opposite the outflow tract to the proximal part of the tail. Absent: 3rd branchial arch. Embryonic age = 8.5 dpc (range 8-9.25 dpc) 8-12 somite pairs | '''Theiler Stage 13 - '''Turning of the embryo. This is a short period with turning initiated in embryos with 6-8 pairs of somites and usually completed in embryos with 14-16 pairs of somites. The first branchial arch has maxillary and mandibular components but the maxillary process is not visible until later (TS16). A second branchial arch is now evident. There is evidence of regionalisation of the heart and the neural tube is closed from a point opposite the outflow tract to the proximal part of the tail. Absent: 3rd branchial arch. Embryonic age = 8.5 dpc (range 8-9.25 dpc) 8-12 somite pairs | ||
'''Neural''' - Formation and closure of anterior neuropore. The rostral extremity of the neural tube closes in embryos with usually about 15-18 somite pairs and defines this stage. The otic pit becomes progressively more indented but not closed, the mandibular process of the 1st branchial arch is clearly visible. The 3rd branchial arch becomes visible late in the stage. | * '''Neural''' - Formation and closure of anterior neuropore. The rostral extremity of the neural tube closes in embryos with usually about 15-18 somite pairs and defines this stage. The otic pit becomes progressively more indented but not closed, the mandibular process of the 1st branchial arch is clearly visible. The 3rd branchial arch becomes visible late in the stage. | ||
'''Limb''' - An increasingly prominent ridge on the lateral body wall, approximately at the level of the 8th-12th somite, indicates the site of the future forelimb bud. Absent: forelimb bud. Embryonic age = 9 dpc (range 8.5-9.75 dpc) 13-20 somite pairs | * '''Limb''' - An increasingly prominent ridge on the lateral body wall, approximately at the level of the 8th-12th somite, indicates the site of the future forelimb bud. Absent: forelimb bud. Embryonic age = 9 dpc (range 8.5-9.75 dpc) 13-20 somite pairs | ||
* '''Heart''' - Heart tube undergoes looping at E8.5. The second heart field (pharyngeal mesoderm cells) contributes to parts of the right ventricle, the interventricular septum, the venous pole, and the base of the outflow tract.{{#pmid:16304598|PMID16304598}} | |||
===Day 9 (E9.0)=== | ===Day 9 (E9.0)=== | ||
:'''Links:''' [[:Category:Mouse E9.0]] |[[:Category:Mouse E9.5]] | :'''Links:''' [[:Category:Mouse E9.0]] | [[:Category:Mouse E9.5]] | ||
[[File:Mouse-E9.0.jpg|left|200px|Mouse E9.0]] | |||
Theiler Stage 14 - Formation of posterior neuropore, forelimb bud. The posterior neuropore forms and the condensation of the forelimb bud becomes apparent near the 8th-12th somite pairs. A distinct condensation of the hind limb bud appears just at the end of the stage.The forebrain vesicle subdivides into telencephalic and diencephalic vesicles. Absent: hindlimb bud, Rathke's pouch. Embryonic age = 9.5 dpc (range 9-10.25 dpc) 21-29 somite pairs | Theiler Stage 14 - Formation of posterior neuropore, forelimb bud. The posterior neuropore forms and the condensation of the forelimb bud becomes apparent near the 8th-12th somite pairs. A distinct condensation of the hind limb bud appears just at the end of the stage.The forebrain vesicle subdivides into telencephalic and diencephalic vesicles. Absent: hindlimb bud, Rathke's pouch. Embryonic age = 9.5 dpc (range 9-10.25 dpc) 21-29 somite pairs | ||
Theiler Stage 15 - Closure of posterior neuropore. Hind limb bud and tail bud. The hind limb bud becomes visible at the level of the 23rd-28th somites. The tail bud appears as a short stump and the 3rd and 4th branchial arches are distinctly concave. Rathke's pouch and the nasal processes start to form. At the end of this stage the posterior neuropore begins to close. Absent: thin and long tail. Embryonic age = 10 dpc (range 9.5-10.75 dpc) 30-34 somite pairs | Theiler Stage 15 - Closure of posterior neuropore. Hind limb bud and tail bud. The hind limb bud becomes visible at the level of the 23rd-28th somites. The tail bud appears as a short stump and the 3rd and 4th branchial arches are distinctly concave. Rathke's pouch and the nasal processes start to form. At the end of this stage the posterior neuropore begins to close. Absent: thin and long tail. Embryonic age = 10 dpc (range 9.5-10.75 dpc) 30-34 somite pairs. | ||
[[Integumentary System Development]] [[Neural Crest Development]] - Melanoblasts precursors derived from the neural crest at around E9.5.{{#pmid:20067551|PMID20067551}} | |||
{| | {| | ||
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| [[File:Primordial germ cell 002 icon.jpg|150px|link=Movie_-_Primordial germ cell migration 02]] | | [[File:Primordial germ cell 002 icon.jpg|150px|link=Movie_-_Primordial germ cell migration 02]] | ||
|- | |- | ||
| [[Movie_-_Primordial germ cell migration 01|Migration E9.0]] | | | [[Movie_-_Primordial germ cell migration 01|Migration E9.0]] | | ||
| [[Movie_-_Primordial germ cell migration 02|Migration E9.5]] | | | [[Movie_-_Primordial germ cell migration 02|Migration E9.5]] | | ||
|} | |} | ||
[[File:Mouse-_embryo_E9.5.jpg]] [[File:Mouse-E9.5.jpg|300px]] | |||
[[File:Mouse E9.5 gene expression.jpg|600px]] | |||
Mouse Stage E9.5 Specific Gene Expression{{#pmid:22174793|PMID22174793}} | |||
===Day 10 (E10.0)=== | ===Day 10 (E10.0)=== | ||
:'''Links:''' [[:Category:Mouse E10]] |[[:Category:Mouse E10.5]] | :'''Links:''' [[:Category:Mouse E10]] | [[:Category:Mouse E10.5]] | ||
Theiler Stage 16 | Theiler Stage 16 | ||
'''Theiler Stage 17''' - Deep Lens Indentation The most obvious distinguishing features are the deepening of the lens pit, with a narrowing of its outer pore-like opening, and the first appearance of the physiological umbilical hernia. The 1st branchial arch is conspicuously divided into maxillary and mandibular components. There is advanced development of the brain tube and the tail elongates and thins. Absent: nasal pits. Embryonic age = 10.5 dpc (range 10-11.25 dpc) 35-39 somite pairs | '''Theiler Stage 17''' - Deep Lens Indentation The most obvious distinguishing features are the deepening of the lens pit, with a narrowing of its outer pore-like opening, and the first appearance of the physiological umbilical hernia. The 1st branchial arch is conspicuously divided into maxillary and mandibular components. There is advanced development of the brain tube and the tail elongates and thins. Absent: nasal pits. Embryonic age = 10.5 dpc (range 10-11.25 dpc) 35-39 somite pairs | ||
[[Integumentary System Development]] {{neural crest}} - Neural crest melanoblasts upregulate early specific markers (Mitf, Tyrosinase, Dct, Kit) E10.5.{{#pmid:20067551|PMID20067551}}> | |||
{{hearing}} - Formation of vestibular (otic) ganglion cells (E10-12) Afferent processes of vestibular ganglion cells invade the macula utricle and saccule and cristae of the semicircular canals (10.5){{#pmid:18298265|PMID18298265}} | |||
{| | |||
| [[File:Mouse-E10.5 ganglia Sox10.jpg|200px]] | |||
| [[Neural Crest Development]] | |||
|- | |||
| [[File:Mouse-Gastrointestinal-tract-E10.5-01.jpg|300px]] | |||
| [[Gastrointestinal Tract Development]] - differential gene expression of some selected markers during development (E10.5 and E13.5) of the mouse gastrointestinal tract.{{#pmid:19300477|PMID19300477}} | |||
|- | |||
| [[File:Primordial germ cell 003 icon.jpg|150px|link=Movie_-_Primordial germ cell migration 03]] | |||
|'''Primordial germ cell migration''' [[Movie_-_Primordial germ cell migration 03|Migration E10.5]] | |||
|} | |||
* '''Heart''' - Cardiac neural crest cells migrate to the outflow tract and endocardial cushions to form the the outflow tract septum (systemic and pulmonary separation).{{#pmid:10725237|PMID10725237}} | |||
[[File:Mouse-_embryo_E10.5.jpg]] [[File:Mouse_CT_E10.5.jpg|200px]] | |||
[[ | [[Renal System Development]] - metanephric mesenchyme present, an area of intermediate mesoderm caudal to the mesonephros and adjacent to a widening of the ‘nephric duct, metanephric portion’ that gives rise to the metanephros.{{#pmid:17452023|PMID17452023}} | ||
[[ | [[File:Mouse embryo E10.5.jpg]] | ||
<gallery> | |||
File:Mouse_E10.5_pecam1.jpg|Pecam 1 staining | |||
File:Mouse_E10.5_pecam1_detail.jpg||Pecam 1 detail staining | |||
File:Mouse_E10.5_smooth_muscle_actin.jpg|Smooth muscle actin staining | |||
File:Mouse_E10.5_smooth_muscle_actin_detail.jpg|Smooth muscle actin detail staining | |||
</gallery> | |||
Pecam 1 and Smooth muscle actin (SMA) staining{{#pmid:22615991|PMID22615991}} | |||
[[File:Mouse E10.5 gene expression.jpg|600px]] | |||
Mouse Stage E10.5 Specific Gene Expression{{#pmid:22174793|PMID22174793}} | |||
===Day 11 (E11.0)=== | ===Day 11 (E11.0)=== | ||
Theiler Stage 18 | :'''Links:''' [[:Category:Mouse E11]] | ||
'''Theiler Stage 18''' | |||
'''Theiler Stage 19''' | |||
{{vision}} - Closure of Lens Vesicle. The primary externally recognisable feature is the progressive closure of the lens vesicle. The somites in the cervical region are no longer visible and the rapid growth of the brain is striking. | |||
{{smell}} - The nasal pits start to form. Absent anterior footplate. Embryonic age = 11 dpc (range 10.5-11.25 dpc) 40-44 somite pairs | |||
{{palate}} - palatal shelves protrude from bilateral maxillary processes. | |||
{{hearing}} - Auditory hillocks absent. Efferent nerve endings first approach hair cells (E11-12)<ref name="PMID18298265"/> | |||
[[Genital_System_Development|Genital System]] - gonad between E11 to E12 differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.{{#pmid:23874228|PMID23874228}} | |||
{{cardiovascular}} - Heart outflow tract supported by the right ventricle, characteristic bend dividing the outflow tract into proximal and distal portions and the distal portion extends to the margins of the pericardial cavity{{#pmid:12923046|PMID12923046}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1767864/figure/f3/ Fig. 3 SEM Heart 42 somites] | |||
===Day 11.5 (E11.5)=== | ===Day 11.5 (E11.5)=== | ||
:'''Links:''' [[:Category:Mouse E11.5]] (TS19) | |||
[[File:Mouse_CT_E11.5.jpg|thumb|left]] | |||
'''Stage 19''' - Lens vesicle completely separated from surface. The lens vesicle becomes completely closed and detached from the ectoderm. The peripheral margins of the eye become well defined. The forelimbs are seen to be divided into two regions, the proximal part consisting of the future limb-girdle and 'arm' and the more peripheral part which forms a circular or paddle-shaped 'handplate' (anterior footplate). The medial and lateral margins of the otic pit are coming together reducing the entrance to a narrow slit and the auditory hillocks become visible. Absent: retinal pigmentation, signs of 'fingers'. Embryonic age = 11.5 dpc (range 11-12.25 dpc) 45-47 somite pairs | '''Stage 19''' - Lens vesicle completely separated from surface. The lens vesicle becomes completely closed and detached from the ectoderm. The peripheral margins of the eye become well defined. The forelimbs are seen to be divided into two regions, the proximal part consisting of the future limb-girdle and 'arm' and the more peripheral part which forms a circular or paddle-shaped 'handplate' (anterior footplate). The medial and lateral margins of the otic pit are coming together reducing the entrance to a narrow slit and the auditory hillocks become visible. Absent: retinal pigmentation, signs of 'fingers'. Embryonic age = 11.5 dpc (range 11-12.25 dpc) 45-47 somite pairs | ||
'''Gonad E11.5''' - coelomic epithelium basement membrane is discontinuous, supporting cell migration. '''11.2-11.4''' - (somite 15-17 stages) coelomic epithelial cells of both sexes migrated into the gonad. In XY gonads, the migrating coelomic epithelial cells became Sertoli cells, as well as interstitial cells. This ability of the coelomic epithelium to give rise to Sertoli cells was developmentally regulated. '''11.5-11.7''' - (somite 18-20 stages) coelomic epithelial cells no longer became Sertoli cells. Instead, cells that migrated into the gonad stayed outside testis cords, in the interstitium. | '''Gonad E11.5''' - coelomic epithelium basement membrane is discontinuous, supporting cell migration. '''11.2-11.4''' - (somite 15-17 stages) coelomic epithelial cells of both sexes migrated into the gonad. In XY gonads, the migrating coelomic epithelial cells became Sertoli cells, as well as interstitial cells. This ability of the coelomic epithelium to give rise to Sertoli cells was developmentally regulated. '''11.5-11.7''' - (somite 18-20 stages) coelomic epithelial cells no longer became Sertoli cells. Instead, cells that migrated into the gonad stayed outside testis cords, in the interstitium.{{#pmid:9808783|PMID9808783}} | ||
'''Aorta-Gonad-Mesonephros E11.5''' - (AGM) region is a site of hematopoietic stem cell (HSC) development prior to colonisation of the embryonic liver. | '''Aorta-Gonad-Mesonephros E11.5''' - (AGM) region is a site of hematopoietic stem cell (HSC) development prior to colonisation of the embryonic liver.{{#pmid:20711982|PMID20711982}} | ||
[[Integumentary_System_-_Tooth_Development|Tooth Development]] - placode stage | [[Integumentary_System_-_Tooth_Development|Tooth Development]] - placode stage | ||
{{mammary gland}} - the thickening and stratified ectodermal milk line breaks up into individual placodes and the underlying mammary mesenchyme begins to condense. Reviewed{{#pmid:18007652<|PMID18007652}} | |||
'''{{heart}}''' - Progressive septation of the outflow tract and septation of the atria and ventricles.{{#pmid:19359541|PMID19359541}} | |||
[[Genital_System_Development|Genital System]] - gonad between E11 to E12 differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.{{#pmid:23874228|PMID23874228}} | |||
[[File:Mouse gonad development timeline.jpg|400px]] | |||
[[File:Mouse-_embryo_E11.5.jpg]] | |||
[[File:Mouse embryo E11.5.jpg|600px]] | |||
[[File:Mouse E11.5 gene expression.jpg|600px]] | |||
Mouse Stage E11.5 Specific Gene Expression{{#pmid:22174793|PMID22174793}} | |||
===Day 12 (E12.0)=== | ===Day 12 (E12.0)=== | ||
:'''Links:''' [[:Category:Mouse E12]] |[[:Category:Mouse E12.5]] | [[File:Tooth_bud_stage.jpg|thumb|Tooth bud stage.]] | ||
:'''Links:''' [[:Category:Mouse E12]] | [[:Category:Mouse E12.5]] | |||
[[File:Mouse_CT_E12.5.jpg|thumb|left]] | |||
Theiler Stage 20 - Earliest signs of fingers. The 'handplate' (anterior footplate) is no longer circular but develops angles which correspond to the future digits. The posterior footplate is also distinguishable from the lower part of the leg. It is possible to see the pigmentation of the pigmented layer of the retina through the transparent cornea. The tongue and brain vesicles are clearly visible. Absent:5 rows of whiskers, indented handplate. Embryonic age = 12 dpc (range 11.5-13 dpc) 48-51 somite pairs | Theiler Stage 20 - Earliest signs of fingers. The 'handplate' (anterior footplate) is no longer circular but develops angles which correspond to the future digits. The posterior footplate is also distinguishable from the lower part of the leg. It is possible to see the pigmentation of the pigmented layer of the retina through the transparent cornea. The tongue and brain vesicles are clearly visible. Absent:5 rows of whiskers, indented handplate. Embryonic age = 12 dpc (range 11.5-13 dpc) 48-51 somite pairs | ||
''' | [[Genital_System_Development|Genital System]] | ||
* '''E11-E12''' gonad differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.{{#pmid:23874228|PMID23874228}} | |||
* '''12.5''' - (somite 30 stage) cell migration finished. Coelomic epithelium basement membrane thickens to form the tunica albuginea.{{#pmid:9808783|PMID9808783}} Leydig cells arise. | |||
* '''12.5-13.5''' - {{oocyte}}s in the ovary enter first meiotic prophase. These arrest later around birth at the diplotene stage (also known as dictyate). | |||
'''Joints''' - 12.5 -13.5 interzone forms in cartilage of digits which is the precursor to synovial joint formation. | '''Joints''' - 12.5 -13.5 interzone forms in cartilage of digits which is the precursor to synovial joint formation. | ||
[[Integumentary_System_-_Tooth_Development|Tooth Development]] - 12.5 bud stage | [[Integumentary_System_-_Tooth_Development|Tooth Development]] - 12.5 bud stage | ||
[[Palate Development]] - E12.5-E14 palatal shelves grow vertically along the developing tongue. | |||
'''Heart''' - E12.5 (TS21) Progressive septation of the outflow tract and initiation of atrioventricular canal septation.{{#pmid:19359541|PMID19359541}} | |||
[[File:Mouse E12.5 gene expression.jpg|600px]] | |||
Mouse Stage E12.5 Specific Gene Expression{{#pmid:22174793|PMID22174793}} | |||
===Day 13 (E13.0)=== | ===Day 13 (E13.0)=== | ||
Line 164: | Line 269: | ||
Theiler Stage 21 - Anterior footplate indented, marked pinna. The distal borders of the anterior and posterior footplates are now indented and the digit widths and locations can be discerned. The 'elbow' and 'wrist' are now identifiable. The pinna rapidly develops and forms a crest at right angles to the head. Five rows of vibrissae are visible as well as a prominant hair follicle over the eye and another over the ear. The lens vesicle has lost its lumen. The physiological umbilical hernia is prominent. Absent: hair follicles, distally separate fingers. Embryonic age = 13 dpc (range 12.5-14) 52-55 somite pairs | Theiler Stage 21 - Anterior footplate indented, marked pinna. The distal borders of the anterior and posterior footplates are now indented and the digit widths and locations can be discerned. The 'elbow' and 'wrist' are now identifiable. The pinna rapidly develops and forms a crest at right angles to the head. Five rows of vibrissae are visible as well as a prominant hair follicle over the eye and another over the ear. The lens vesicle has lost its lumen. The physiological umbilical hernia is prominent. Absent: hair follicles, distally separate fingers. Embryonic age = 13 dpc (range 12.5-14) 52-55 somite pairs | ||
'''Ovary''' - E13.5-16.5 ovarian cord structure formation required for oocyte development | '''Ovary''' - E13.5-16.5 ovarian cord structure formation required for oocyte development{{#pmid:20064216|PMID20064216}} | ||
'''Liver''' - E13.5-15.5 single layer of hepatoblasts forms close to the portal mesenchyme (ductal plate) and expresses bile duct-specific cytokeratins. By E16.5, the ductal plate partially becomes bi-layered and, around E17.5, enters a phase of profound remodeling during which time focal dilations appear between the two cell layers. | '''Liver''' - E13.5-15.5 single layer of hepatoblasts forms close to the portal mesenchyme (ductal plate) and expresses bile duct-specific cytokeratins. By E16.5, the ductal plate partially becomes bi-layered and, around E17.5, enters a phase of profound remodeling during which time focal dilations appear between the two cell layers. | ||
[[Sensory_-_Hearing_and_Balance_Development|Hearing and Balance]] - Peak hair cell mitosis in crista ampullaris, maculae of saccules, and utricles (E13-17){{#pmid:18298265|PMID18298265}} | |||
'''Gastrointestinal tract''' - differential gene expression of some selected markers during development (E10.5 and E13.5) of the mouse gastrointestinal tract. | '''Gastrointestinal tract''' - differential gene expression of some selected markers during development (E10.5 and E13.5) of the mouse gastrointestinal tract.{{#pmid:19300477|PMID19300477}} | ||
[[File:Mouse-Gastrointestinal-tract-E13.5-01.jpg|600px]] | [[File:Mouse-Gastrointestinal-tract-E13.5-01.jpg|600px]] | ||
{{#pmid:19359541|PMID19359541}} | |||
'''Heart''' - E13.5 (TS22) Bilaterally asymmetrical aortic arch system, completely septated outflow tract and ventricles and remodeling of the atrioventricular cushions.{{#pmid:19359541|PMI19359541}} | |||
[[File:Mouse E13.5 gene expression.jpg|600px]] | |||
Mouse Stage E13.5 Specific Gene Expression{{#pmid:22174793|PMID22174793}} | |||
===Day 14 (E14.0)=== | ===Day 14 (E14.0)=== | ||
[[File:Mouse embryo E14 microCT icon.jpg|thumb|left|Mouse embryo E14 microCT]] | |||
:'''Links:''' [[:Category:Mouse E14]] | |||
Theiler Stage 22 - Fingers separate distally. Individual 'fingers' are visible in the anterior footplate and there are deep indentations between the 'toes' which are not yet separated.The long bones of the limbs are present and there are hair follicles in the pectoral, pelvic and trunk regions. The pinna is turned forwards and the umbilical hernia is conspicuous. Absent: hair follicles in the cephalic region. Embryonic age = 14 dpc (range 13.5-15 dpc) 56-60 somite pairs | Theiler Stage 22 - Fingers separate distally. Individual 'fingers' are visible in the anterior footplate and there are deep indentations between the 'toes' which are not yet separated.The long bones of the limbs are present and there are hair follicles in the pectoral, pelvic and trunk regions. The pinna is turned forwards and the umbilical hernia is conspicuous. Absent: hair follicles in the cephalic region. Embryonic age = 14 dpc (range 13.5-15 dpc) 56-60 somite pairs | ||
[[Endocrine_-_Thyroid_Development|Thyroid]] ultimobranchial body (UBB) and thyroid primordium fuse and give rise to calcitonin-producing C cells and thyroglobulin-producing follicular cells, respectively. | [[Endocrine_-_Thyroid_Development|Thyroid]] ultimobranchial body (UBB) and thyroid primordium fuse and give rise to calcitonin-producing C cells and thyroglobulin-producing follicular cells, respectively.{{#pmid:20697379|PMID20697379}} | ||
[[Integumentary_System_-_Tooth_Development|Tooth Development]] - cap stage | [[Integumentary_System_-_Tooth_Development|Tooth Development]] - cap stage | ||
[[Palate Development]] - E14.5 palatal shelves elevate, meet, and fuse at the midline, to form an intact palate shelf. | |||
[[Lymph Node Development]] - initiated normally at E14.5{{#pmid:19060331|PMID19060331}} | |||
'''Heart''' - E14.5 (TS23) Atrial septation complete.{{#pmid:19359541|PMID19359541}} | |||
== Week 3 == | == Week 3 == | ||
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Toes separate. The 'toes' separate and are clearly divergent, not becoming parallel until later. Hair follicles are present in the cephalic region but not at the periphery of the vibrissae. The pinna covers more than half of the external auditory meatus and the eyelids are still open. Absent: nail primordia, 'fingers' 2-5 parallel. Embryonic age = 15 dpc >60 somite pairs | Toes separate. The 'toes' separate and are clearly divergent, not becoming parallel until later. Hair follicles are present in the cephalic region but not at the periphery of the vibrissae. The pinna covers more than half of the external auditory meatus and the eyelids are still open. Absent: nail primordia, 'fingers' 2-5 parallel. Embryonic age = 15 dpc >60 somite pairs | ||
[[Sensory_-_Hearing_and_Balance_Development|Hearing and Balance]] - Afferent synaptogenesis with hair cells begins (E15)<ref name="PMID18298265"/> | |||
[[Integumentary_System_-_Tooth_Development|Tooth Development]] - bell stage | [[Integumentary_System_-_Tooth_Development|Tooth Development]] - bell stage | ||
[[Integumentary System - Mammary Gland Development|Mammary Development]] E15.5 - mammary epithelium begins to proliferate at the tip and the primary sprout pushes through the mammary mesenchyme towards the underlying fat pad. Reviewed{{#pmid:18007652|PMID18007652}} | |||
===Day 16 (E16.0)=== | ===Day 16 (E16.0)=== | ||
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Reposition of umbilical hernia 'Fingers' 2-5 are nearly parallel. Nail primordia are visible on the 'toes'. The eyelids have fused in most cases by the end of the stage and the pinna almost completely covers the external auditory meatus. The umbilical hernia is disappearing and there is a corresponding increase in the size of the peritoneal sac. Absent: 'fingers' and 'toes' joined together. Embryonic age = 16 dpc > 60 Somite pairs | Reposition of umbilical hernia 'Fingers' 2-5 are nearly parallel. Nail primordia are visible on the 'toes'. The eyelids have fused in most cases by the end of the stage and the pinna almost completely covers the external auditory meatus. The umbilical hernia is disappearing and there is a corresponding increase in the size of the peritoneal sac. Absent: 'fingers' and 'toes' joined together. Embryonic age = 16 dpc > 60 Somite pairs | ||
'''Liver''' - E16.5 ductal plate becomes partially bi-layered. | '''Heart''' - E15.5 (TS24) - E18.5 (TS27) Definitive external prenatal configuration achieved, Atrioventricular valve leaflets are being modified, Coronary arteries are being modified.{{#pmid:19359541|PMID19359541}} | ||
'''Liver''' - E16.5 ductal plate becomes partially bi-layered. | |||
===Day 17 (E17.0)=== | ===Day 17 (E17.0)=== | ||
Theiler Stage 25 | {| | ||
| [[File:Mouse-E17.5.jpg|200px|Mouse-E17.5]] | |||
| Theiler Stage 25 | |||
'''Skin wrinkled''' The skin has thickened and formed wrinkles and the subcutaneous veins are less visible. The 'fingers' and 'toes' have become parallel and the umbilical hernia has disappeared. The eyelids have fused. Whiskers are just visible. Absent: ear extending over auditory meatus, long whiskers. Embryonic age = 17 dpc | '''Skin wrinkled''' The skin has thickened and formed wrinkles and the subcutaneous veins are less visible. The 'fingers' and 'toes' have become parallel and the umbilical hernia has disappeared. The eyelids have fused. Whiskers are just visible. Absent: ear extending over auditory meatus, long whiskers. Embryonic age = 17 dpc | ||
'''Liver''' - E17.5 bilayered ductal plate remodelled with focal dilations between the two cell layers.'''Prostate''' - E17.5 urogenital sinus epithelial cells grow into mesenchyme to form prostate buds. | '''Liver''' - E17.5 bilayered ductal plate remodelled with focal dilations between the two cell layers. | ||
'''Prostate''' - E17.5 urogenital sinus epithelial cells grow into mesenchyme to form prostate buds. | |||
|} | |||
===Day 18 (E18.0)=== | ===Day 18 (E18.0)=== | ||
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'''Long whiskers''' The whiskers that were present at stage 25 are definitely longer and the skin has thickened. The pinna is larger and such that virtually none of the lumen of the auditory meatus is visible. The eyes are barely visible through the closed eyelids. Embryonic age = 18 dpc | '''Long whiskers''' The whiskers that were present at stage 25 are definitely longer and the skin has thickened. The pinna is larger and such that virtually none of the lumen of the auditory meatus is visible. The eyes are barely visible through the closed eyelids. Embryonic age = 18 dpc | ||
[[Sensory_-_Hearing_and_Balance_Development|Hearing and Balance]] - Morphological differentiation into Type I and Type II hair cells (E18-P10)<ref name="PMID18298265"/> | |||
[[Integumentary System Development]] - Langerhans cells (LCs) precursors recruited into the epidermis in a single wave around E18 and acquired a dendritic morphology.{{#pmid:19995948|PMID19995948}} | |||
[[Integumentary System - Mammary Gland Development|Mammary Development]] - E18.5 elongating duct has now grown into the fat pad and has branched into a small ductal system. Cells of the mammary mesenchyme have formed the nipple, which is made of specialized epidermal cells. Reviewed{{#pmid:18007652|PMID18007652}} | |||
===Day 19 (E19.0)=== | ===Day 19 (E19.0)=== | ||
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===Day 21 (E21.0)=== | ===Day 21 (E21.0)=== | ||
[[Sensory_-_Hearing_and_Balance_Development|Hearing and Balance]] - Fully mature morphological and physiological innervation of vestibular system (P28)<ref name="PMID18298265"/> | |||
== Table Data == | === Table Data === | ||
The main table data is modified from several different sources<ref | The main table data is modified from several different sources<ref name="The House Mouse">{{Ref-Theiler1972}}</ref> | ||
{{#pmid:8269852|PMID8269852}} and includes additional sources as listed within the table. | |||
== | ==Postnatal== | ||
The | ===P2 to P4=== | ||
Hair begins to appear | |||
===P3 to P5=== | |||
Ears open | |||
===P5 to P7=== | |||
Uterine adenogenesis - uterine gland buds develop.<ref>Shelton DN, Fornalik H, Neff T, Park SY, Bender D, et al. (2012) The Role of LEF1 in Endometrial Gland Formation and Carcinogenesis. [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040312 PLoS ONE] 7(7): e40312. doi:10.1371/journal.pone.0040312</ref> | |||
===P11 to P12=== | |||
Eyes open. | |||
==Species Stages Comparison == | |||
The tables below gives an approximate comparison of human, mouse, rat and other embryos based upon Carnegie staging. There are also comparisons of different models and system development. | |||
===Embryonic Age=== | |||
{{CarnegieComparisonHRM}} | |||
===Model Comparison=== | |||
{{Mouse Rat Pig table}} | |||
===Respiratory Development=== | |||
{{Respiratory Species Comparison table}} | |||
==Timed Pregnancy== | ==Timed Pregnancy== | ||
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* Noon of the day on which the vaginal plug is found the embryos are aged "0.5 dpc" (days post coitum). | * Noon of the day on which the vaginal plug is found the embryos are aged "0.5 dpc" (days post coitum). | ||
* Noon on the next day, the embryos are 1.5 dpc, and so on. | * Noon on the next day, the embryos are 1.5 dpc, and so on. | ||
==References== | ==References== | ||
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== External Links == | == External Links == | ||
{{ External Links}} | |||
* '''Edinburgh Mouse Atlas of Gene Expression''' - [http://genex.hgu.mrc.ac.uk/Documentation/Emage/Course/emage/Appendix4.html Edinburgh Mouse Atlas of Gene Expression- Appendix 4 Theiler Staging] | [http://genex.hgu.mrc.ac.uk/Databases/Anatomy/MAstaging.shtml The Edinburgh Mouse Atlas: Staging Criteria] | [http://genex.hgu.mrc.ac.uk/Databases/Anatomy/new/ Standard Anatomical Nomenclature ] | * '''Edinburgh Mouse Atlas of Gene Expression''' - [http://genex.hgu.mrc.ac.uk/Documentation/Emage/Course/emage/Appendix4.html Edinburgh Mouse Atlas of Gene Expression- Appendix 4 Theiler Staging] | [http://genex.hgu.mrc.ac.uk/Databases/Anatomy/MAstaging.shtml The Edinburgh Mouse Atlas: Staging Criteria] | [http://genex.hgu.mrc.ac.uk/Databases/Anatomy/new/ Standard Anatomical Nomenclature ] | ||
{{ | ---- | ||
{{Animals}} | |||
{{Glossary}} | |||
{{ | {{Footer}} | ||
[[Category:Mouse]] [[Category:Timeline]] | [[Category:Mouse]] [[Category:Timeline]] |
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Introduction
This mouse page is organised to show a detailed day by day development of sytems and features with approximate timing of key events. The staging by "days" relate to in the female presence of a vaginal plug indicating that the mating occurred, see timed pregnancy.
Theiler Stages divides mouse development into 26 prenatal and 2 postnatal stages.[1]
Downs and Davies Stages is a more recent (1993) staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope.[2]
There have been early online atlas[3] and several new staging papers and online atlases released.[4][5]
Mouse Links: Introduction | Mouse Stages | Mouse Timeline | Mouse Timeline Detailed | Mouse Estrous Cycle | Mouse Heart | Mouse Knockout | Movie - Cephalic Plexus | Movie - Blastocyst Cdx2 | ANAT2341 Project 2009 | Category:Mouse | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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- Mouse Stages: E1 | E2.5 | E3.0 | E3.5 | E4.5 | E5.0 | E5.5 | E6.0 | E7.0 | E7.5 | E8.0 | E8.5 | E9.0 | E9.5 | E10 | E10.5 | E11 | E11.5 | E12 | E12.5 | E13 | E13.5 | E14 | E14.5 | E15 | E15.5 | E16 | E16.5 | E17 | E17.5 | E18 | E18.5 | E19 | E20 | Timeline | About timed pregnancy
Carnegie | Stage | |||||||||||||||||||||||
Human | Days | 1 | 2-3 | 4-5 | 5-6 | 7-12 | 13-15 | 15-17 | 17-19 | 20 | 22 | 24 | 28 | 30 | 33 | 36 | 40 | 42 | 44 | 48 | 52 | 54 | 55 | 58 |
Mouse | Days | 1 | 2 | 3 | E4.5 | E5.0 | E6.0 | E7.0 | E8.0 | E9.0 | E9.5 | E10 | E10.5 | E11 | E11.5 | E12 | E12.5 | E13 | E13.5 | E14 | E14.5 | E15 | E15.5 | E16 |
Rat | Days | 1 | 3.5 | 4-5 | 5 | 6 | 7.5 | 8.5 | 9 | 10.5 | 11 | 11.5 | 12 | 12.5 | 13 | 13.5 | 14 | 14.5 | 15 | 15.5 | 16 | 16.5 | 17 | 17.5 |
Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison | ||||||||||||||||||||||||
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Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | Medaka | Category:Timeline |
Week 1
Day 1 (E1.0)
Theiler Stage 1 - Fertilization
Theiler Stage 2 - Dividing egg stage 2-4 cells. Zona pellucida present. First cleavage occurs at about 24 hours. Embryonic age = 1 dpc (range 1-2.5 dpc)
Day 2 (E2.0)
Theiler Stage 3 - Morula (early to fully compacted) 4-16 cells. Zona pellucida present. Usually found in the oviduct towards the utero-tubal junction. Embryonic age = 2 dpc (range 1-3.5 dpc)
Day 3 (E3.0)
Theiler Stage 4 - Blastocyst (ICM apparent) 16-40 compacted cells. Zona pellucida present. Embryo progresses from morula to the blastocyst. Early evidence of the blastocoelic cavity.
In the blastocyst stage (zona-intact) there is a distinct inner cell mass and an outer layer of trophectoderm cells. Usually located in the uterine lumen. Embryonic age = 3 dpc (range 2-4 dpc)
Day 4 (E4.0)
Theiler Stage 5 - Blastocyst (Zona pellucida absent) Zona free blastocyst. Invariably located within the uterine lumen.
Embryonic age = 4 dpc (range 3-5.5 dpc)
Theiler Stage 6 - Attachment of blastocyst. Blastocyst implants, first evidence of embryonic endoderm cells covering the blastocoelic surface of the inner cell mass. Embryonic age = 4.5 dpc (range 4-5.5 dpc)
Day 5 (E5.0)
Theiler Stage 7 - Implantation and formation of egg cylinder. Ectoplacental cone appears. Rapid increase in the number of inner cell mass cells leading to the formation of the epiblast with subsequent growth to form the egg cylinder. The proximal or visceral cells (opposite side from the trophoblastic cap) are cuboidal in shape. Primary endoderm lines the mural trophectoderm. Embryonic age = 5 dpc (range 4.5-6 dpc)
Differentiation of egg cylinder. Implantation site 2x3mm.The maternal tissue is invaded by trophoblast (primary) giant cells and the ectoplacental cone is invaded by maternal blood. Differentiation of the egg cylinder into embryonic and extra-embryonic regions and the formation of the pro-amniotic cavity. Reichert's membrane, which is non-cellular and secreted by the distal endoderm, first appears. Embryonic age = 6 dpc (range 5-6.5 dpc)
Day 5 (E5.5)
E5.5 Nodal signaling from the epiblast induces distal visceral endoderm (DVE) formation that will establish embryo anterior–posterior axis.[6]
Theiler Stage 8
Day 6 (E6.0)
Theiler Stage 9
Stage 9a Advanced Endometrial Reaction. Advanced egg-cylinder stage with the first evidence of an embryonic axis. Clear morphological distinction between the embryonic and extra-embryonic ectoderm. The ectoplacental cone is further invaded by maternal blood and the original lumen of the uterine crypt has disappeared. Equivalent Downs and Davies Stage : PS (pre-streak)
Stage 9b Advanced Endometrial Reaction. Late in this stage gastrulation begins, producing the first mesodermal cells. Equivalent Downs and Davies Stage : ES (early streak)
Day 6.5 (E6.5)
- Heart - earliest heart precursors are 50 founder cells located on both sides of the midline in the epiblast of early gastrula stage embryos [7]
Day 7 (E7.0)
Theiler Stage 10
Stage 10a Amnion. Tissue at the posterior end of the primitive streak bulges into the pro-amniotic cavity and forms the amniotic fold (Equivalent Downs and Davies stage: MS, mid-streak)
Stage 10b Amnion. In the mesoderm of the posterior amniotic fold small cavities coalesce to form a single cavity, the exocoelom Embryonic age = 7.0 dpc (range 6.5-7.5 dpc)
Stage 10c . Amnion. The allantoic bud first appears, gastrulation continues and the node becomes visible. Embryonic age = 7.0 dpc (range 6.5-7.5 dpc) (Equivalent Downs and Davies stages: MS - LS, mid-streak to late streak)
Day 7 (E7.5)
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E7.5 early bud[8] | E7.5 late bud[8] |
Theiler Stage 11
Stage 11a Neural Plate, Presomite stage The amniotic cavity is now sealed off into three distinct cavities - the amniotic cavity, the exocoelom and the ectoplacental cleft. The neural plate is defined anteriorly and the head process is developing. In the midline, subjacent to the neural groove, the notochodal plate is visible. Embryonic age = 7.5 dpc (range 7.25-8 dpc) Equivalent Downs and Davies stages: OB-EB (no allantoic bud to early allantoic bud); LB-EHF-LHF (late allantoic bud to early head fold to late head fold)
Stage 11b Neural Plate, Presomite stage. The allantoic bud elongates. Embryonic age = 7.5 dpc (range 7.25-8 dpc) . Equivalent Downs & Davies stages: OB-EB (no allantoic bud to early allantoic bud); LB-EHF-LHF (late allantoic bud to early head fold to late head fold)
Stage 11c Neural Plate, Presomite stage. The rostral part of the neural plate begins to enlarge to form the head folds. The neural groove is visible. Embryonic age = 7.5 dpc (range 7.25-8 dpc) Equivalent Downs and Davies stages: OB-EB (no allantoic bud to early allantoic bud); LB-EHF-LHF (late allantoic bud to early head fold to late head fold)
Stage11d Neural Plate, Presomite stage. Head folds continue to enlarge and the foregut pocket begins to form. Embryonic age = 7.5 dpc (range 7.25-8 dpc) ; LB-EHF-LHF (late allantoic bud to early head fold to late head fold) . Equivalent Downs & Davies stages: OB-EB (no allantoic bud to early allantoic bud)
Week 2
Day 8 (E8.0)
- Links: Category:Mouse E8.0 | Category:Mouse E8.5
Theiler Stage 12
Theiler Stage 12a - First Somites Unturned embryo with first appearance of somite pairs 1-4 somites. The allantois extends further into the exocoelom and the maxillary components of the 1st branchial arch become prominent. The preotic sulcus is visible in the 2-3 somite embryo. The cardiogenic plate begins to form and the foregut pocket is clearly visible. Embryonic age = 8 dpc (range 7.5-8.75 dpc) 1-7 somite pairs
Theiler Stage 12b - First Somites Unturned embryo with first appearance of somite pairs 5-7 somites. The headfolds are particularly prominent and neural closure occurs in the region of the 4th and 5th somites, extending in both directions from this site. The otic placode appears at 9 somite pairs stage (between E8.5 to 8.75). The optic placodes are first evident and become indented to form the optic pits. The heart rudiment develops rapidly. The allantois contacts the chorion at the end of this stage. Absent: The 2nd branchial arch and >7 somites. Embryonic age = 8 dpc (range 7.5-8.75 dpc) 1-7 somite pairs
Theiler Stage 13 - Turning of the embryo. This is a short period with turning initiated in embryos with 6-8 pairs of somites and usually completed in embryos with 14-16 pairs of somites. The first branchial arch has maxillary and mandibular components but the maxillary process is not visible until later (TS16). A second branchial arch is now evident. There is evidence of regionalisation of the heart and the neural tube is closed from a point opposite the outflow tract to the proximal part of the tail. Absent: 3rd branchial arch. Embryonic age = 8.5 dpc (range 8-9.25 dpc) 8-12 somite pairs
- Neural - Formation and closure of anterior neuropore. The rostral extremity of the neural tube closes in embryos with usually about 15-18 somite pairs and defines this stage. The otic pit becomes progressively more indented but not closed, the mandibular process of the 1st branchial arch is clearly visible. The 3rd branchial arch becomes visible late in the stage.
- Limb - An increasingly prominent ridge on the lateral body wall, approximately at the level of the 8th-12th somite, indicates the site of the future forelimb bud. Absent: forelimb bud. Embryonic age = 9 dpc (range 8.5-9.75 dpc) 13-20 somite pairs
- Heart - Heart tube undergoes looping at E8.5. The second heart field (pharyngeal mesoderm cells) contributes to parts of the right ventricle, the interventricular septum, the venous pole, and the base of the outflow tract.[9]
Day 9 (E9.0)
- Links: Category:Mouse E9.0 | Category:Mouse E9.5
Theiler Stage 14 - Formation of posterior neuropore, forelimb bud. The posterior neuropore forms and the condensation of the forelimb bud becomes apparent near the 8th-12th somite pairs. A distinct condensation of the hind limb bud appears just at the end of the stage.The forebrain vesicle subdivides into telencephalic and diencephalic vesicles. Absent: hindlimb bud, Rathke's pouch. Embryonic age = 9.5 dpc (range 9-10.25 dpc) 21-29 somite pairs
Theiler Stage 15 - Closure of posterior neuropore. Hind limb bud and tail bud. The hind limb bud becomes visible at the level of the 23rd-28th somites. The tail bud appears as a short stump and the 3rd and 4th branchial arches are distinctly concave. Rathke's pouch and the nasal processes start to form. At the end of this stage the posterior neuropore begins to close. Absent: thin and long tail. Embryonic age = 10 dpc (range 9.5-10.75 dpc) 30-34 somite pairs.
Integumentary System Development Neural Crest Development - Melanoblasts precursors derived from the neural crest at around E9.5.[10]
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Migration E9.0 | | Migration E9.5 | |
Mouse Stage E9.5 Specific Gene Expression[11]
Day 10 (E10.0)
- Links: Category:Mouse E10 | Category:Mouse E10.5
Theiler Stage 16
Theiler Stage 17 - Deep Lens Indentation The most obvious distinguishing features are the deepening of the lens pit, with a narrowing of its outer pore-like opening, and the first appearance of the physiological umbilical hernia. The 1st branchial arch is conspicuously divided into maxillary and mandibular components. There is advanced development of the brain tube and the tail elongates and thins. Absent: nasal pits. Embryonic age = 10.5 dpc (range 10-11.25 dpc) 35-39 somite pairs
Integumentary System Development neural crest - Neural crest melanoblasts upregulate early specific markers (Mitf, Tyrosinase, Dct, Kit) E10.5.[10]>
hearing - Formation of vestibular (otic) ganglion cells (E10-12) Afferent processes of vestibular ganglion cells invade the macula utricle and saccule and cristae of the semicircular canals (10.5)[12]
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Neural Crest Development |
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Gastrointestinal Tract Development - differential gene expression of some selected markers during development (E10.5 and E13.5) of the mouse gastrointestinal tract.[13] |
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Primordial germ cell migration Migration E10.5 |
- Heart - Cardiac neural crest cells migrate to the outflow tract and endocardial cushions to form the the outflow tract septum (systemic and pulmonary separation).[14]
Renal System Development - metanephric mesenchyme present, an area of intermediate mesoderm caudal to the mesonephros and adjacent to a widening of the ‘nephric duct, metanephric portion’ that gives rise to the metanephros.[15]
Pecam 1 and Smooth muscle actin (SMA) staining[16]
Mouse Stage E10.5 Specific Gene Expression[11]
Day 11 (E11.0)
- Links: Category:Mouse E11
Theiler Stage 18
Theiler Stage 19
vision - Closure of Lens Vesicle. The primary externally recognisable feature is the progressive closure of the lens vesicle. The somites in the cervical region are no longer visible and the rapid growth of the brain is striking.
smell - The nasal pits start to form. Absent anterior footplate. Embryonic age = 11 dpc (range 10.5-11.25 dpc) 40-44 somite pairs
palate - palatal shelves protrude from bilateral maxillary processes.
hearing - Auditory hillocks absent. Efferent nerve endings first approach hair cells (E11-12)[12]
Genital System - gonad between E11 to E12 differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.[17]
cardiovascular - Heart outflow tract supported by the right ventricle, characteristic bend dividing the outflow tract into proximal and distal portions and the distal portion extends to the margins of the pericardial cavity[18] Fig. 3 SEM Heart 42 somites
Day 11.5 (E11.5)
- Links: Category:Mouse E11.5 (TS19)
Stage 19 - Lens vesicle completely separated from surface. The lens vesicle becomes completely closed and detached from the ectoderm. The peripheral margins of the eye become well defined. The forelimbs are seen to be divided into two regions, the proximal part consisting of the future limb-girdle and 'arm' and the more peripheral part which forms a circular or paddle-shaped 'handplate' (anterior footplate). The medial and lateral margins of the otic pit are coming together reducing the entrance to a narrow slit and the auditory hillocks become visible. Absent: retinal pigmentation, signs of 'fingers'. Embryonic age = 11.5 dpc (range 11-12.25 dpc) 45-47 somite pairs
Gonad E11.5 - coelomic epithelium basement membrane is discontinuous, supporting cell migration. 11.2-11.4 - (somite 15-17 stages) coelomic epithelial cells of both sexes migrated into the gonad. In XY gonads, the migrating coelomic epithelial cells became Sertoli cells, as well as interstitial cells. This ability of the coelomic epithelium to give rise to Sertoli cells was developmentally regulated. 11.5-11.7 - (somite 18-20 stages) coelomic epithelial cells no longer became Sertoli cells. Instead, cells that migrated into the gonad stayed outside testis cords, in the interstitium.[19]
Aorta-Gonad-Mesonephros E11.5 - (AGM) region is a site of hematopoietic stem cell (HSC) development prior to colonisation of the embryonic liver.[20]
Tooth Development - placode stage
mammary gland - the thickening and stratified ectodermal milk line breaks up into individual placodes and the underlying mammary mesenchyme begins to condense. ReviewedPubmedParser error: Invalid PMID, please check. (PMID: < 18007652<)
heart - Progressive septation of the outflow tract and septation of the atria and ventricles.[21]
Genital System - gonad between E11 to E12 differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.[17]
Mouse Stage E11.5 Specific Gene Expression[11]
Day 12 (E12.0)
- Links: Category:Mouse E12 | Category:Mouse E12.5
Theiler Stage 20 - Earliest signs of fingers. The 'handplate' (anterior footplate) is no longer circular but develops angles which correspond to the future digits. The posterior footplate is also distinguishable from the lower part of the leg. It is possible to see the pigmentation of the pigmented layer of the retina through the transparent cornea. The tongue and brain vesicles are clearly visible. Absent:5 rows of whiskers, indented handplate. Embryonic age = 12 dpc (range 11.5-13 dpc) 48-51 somite pairs
- E11-E12 gonad differentiates from a bipotential to sexually-differentiated state, based upon transcriptome analysis.[17]
- 12.5 - (somite 30 stage) cell migration finished. Coelomic epithelium basement membrane thickens to form the tunica albuginea.[19] Leydig cells arise.
- 12.5-13.5 - oocytes in the ovary enter first meiotic prophase. These arrest later around birth at the diplotene stage (also known as dictyate).
Joints - 12.5 -13.5 interzone forms in cartilage of digits which is the precursor to synovial joint formation.
Tooth Development - 12.5 bud stage
Palate Development - E12.5-E14 palatal shelves grow vertically along the developing tongue.
Heart - E12.5 (TS21) Progressive septation of the outflow tract and initiation of atrioventricular canal septation.[21]
Mouse Stage E12.5 Specific Gene Expression[11]
Day 13 (E13.0)
- Links: Category:Mouse E13 | Category:Mouse E13.5
Theiler Stage 21 - Anterior footplate indented, marked pinna. The distal borders of the anterior and posterior footplates are now indented and the digit widths and locations can be discerned. The 'elbow' and 'wrist' are now identifiable. The pinna rapidly develops and forms a crest at right angles to the head. Five rows of vibrissae are visible as well as a prominant hair follicle over the eye and another over the ear. The lens vesicle has lost its lumen. The physiological umbilical hernia is prominent. Absent: hair follicles, distally separate fingers. Embryonic age = 13 dpc (range 12.5-14) 52-55 somite pairs
Ovary - E13.5-16.5 ovarian cord structure formation required for oocyte development[22]
Liver - E13.5-15.5 single layer of hepatoblasts forms close to the portal mesenchyme (ductal plate) and expresses bile duct-specific cytokeratins. By E16.5, the ductal plate partially becomes bi-layered and, around E17.5, enters a phase of profound remodeling during which time focal dilations appear between the two cell layers.
Hearing and Balance - Peak hair cell mitosis in crista ampullaris, maculae of saccules, and utricles (E13-17)[12]
Gastrointestinal tract - differential gene expression of some selected markers during development (E10.5 and E13.5) of the mouse gastrointestinal tract.[13]
Heart - E13.5 (TS22) Bilaterally asymmetrical aortic arch system, completely septated outflow tract and ventricles and remodeling of the atrioventricular cushions.[23]
Mouse Stage E13.5 Specific Gene Expression[11]
Day 14 (E14.0)
- Links: Category:Mouse E14
Theiler Stage 22 - Fingers separate distally. Individual 'fingers' are visible in the anterior footplate and there are deep indentations between the 'toes' which are not yet separated.The long bones of the limbs are present and there are hair follicles in the pectoral, pelvic and trunk regions. The pinna is turned forwards and the umbilical hernia is conspicuous. Absent: hair follicles in the cephalic region. Embryonic age = 14 dpc (range 13.5-15 dpc) 56-60 somite pairs
Thyroid ultimobranchial body (UBB) and thyroid primordium fuse and give rise to calcitonin-producing C cells and thyroglobulin-producing follicular cells, respectively.[24]
Tooth Development - cap stage
Palate Development - E14.5 palatal shelves elevate, meet, and fuse at the midline, to form an intact palate shelf.
Lymph Node Development - initiated normally at E14.5[25]
Heart - E14.5 (TS23) Atrial septation complete.[21]
Week 3
Day 15 (E15.0)
Theiler Stage 23 Toes separate. The 'toes' separate and are clearly divergent, not becoming parallel until later. Hair follicles are present in the cephalic region but not at the periphery of the vibrissae. The pinna covers more than half of the external auditory meatus and the eyelids are still open. Absent: nail primordia, 'fingers' 2-5 parallel. Embryonic age = 15 dpc >60 somite pairs
Hearing and Balance - Afferent synaptogenesis with hair cells begins (E15)[12]
Tooth Development - bell stage
Mammary Development E15.5 - mammary epithelium begins to proliferate at the tip and the primary sprout pushes through the mammary mesenchyme towards the underlying fat pad. Reviewed[26]
Day 16 (E16.0)
Theiler Stage 24 Reposition of umbilical hernia 'Fingers' 2-5 are nearly parallel. Nail primordia are visible on the 'toes'. The eyelids have fused in most cases by the end of the stage and the pinna almost completely covers the external auditory meatus. The umbilical hernia is disappearing and there is a corresponding increase in the size of the peritoneal sac. Absent: 'fingers' and 'toes' joined together. Embryonic age = 16 dpc > 60 Somite pairs
Heart - E15.5 (TS24) - E18.5 (TS27) Definitive external prenatal configuration achieved, Atrioventricular valve leaflets are being modified, Coronary arteries are being modified.[21]
Liver - E16.5 ductal plate becomes partially bi-layered.
Day 17 (E17.0)
Day 18 (E18.0)
Theiler Stage 26
Long whiskers The whiskers that were present at stage 25 are definitely longer and the skin has thickened. The pinna is larger and such that virtually none of the lumen of the auditory meatus is visible. The eyes are barely visible through the closed eyelids. Embryonic age = 18 dpc
Hearing and Balance - Morphological differentiation into Type I and Type II hair cells (E18-P10)[12]
Integumentary System Development - Langerhans cells (LCs) precursors recruited into the epidermis in a single wave around E18 and acquired a dendritic morphology.[27]
Mammary Development - E18.5 elongating duct has now grown into the fat pad and has branched into a small ductal system. Cells of the mammary mesenchyme have formed the nipple, which is made of specialized epidermal cells. Reviewed[26]
Day 19 (E19.0)
Theiler Stage 27
Theiler Stage 28 New born Mouse
Post-natal development
Day 20 (E20.0)
Day 21 (E21.0)
Hearing and Balance - Fully mature morphological and physiological innervation of vestibular system (P28)[12]
Table Data
The main table data is modified from several different sources[1] [2] and includes additional sources as listed within the table.
Postnatal
P2 to P4
Hair begins to appear
P3 to P5
Ears open
P5 to P7
Uterine adenogenesis - uterine gland buds develop.[28]
P11 to P12
Eyes open.
Species Stages Comparison
The tables below gives an approximate comparison of human, mouse, rat and other embryos based upon Carnegie staging. There are also comparisons of different models and system development.
Embryonic Age
Carnegie | Stage | |||||||||||||||||||||||
Human | Days | 1 | 2-3 | 4-5 | 5-6 | 7-12 | 13-15 | 15-17 | 17-19 | 20 | 22 | 24 | 28 | 30 | 33 | 36 | 40 | 42 | 44 | 48 | 52 | 54 | 55 | 58 |
Mouse | Days | 1 | 2 | 3 | E4.5 | E5.0 | E6.0 | E7.0 | E8.0 | E9.0 | E9.5 | E10 | E10.5 | E11 | E11.5 | E12 | E12.5 | E13 | E13.5 | E14 | E14.5 | E15 | E15.5 | E16 |
Rat | Days | 1 | 3.5 | 4-5 | 5 | 6 | 7.5 | 8.5 | 9 | 10.5 | 11 | 11.5 | 12 | 12.5 | 13 | 13.5 | 14 | 14.5 | 15 | 15.5 | 16 | 16.5 | 17 | 17.5 |
Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison | ||||||||||||||||||||||||
|
Model Comparison
Postnatal Animal Models | mouse | rat | pig |
---|---|---|---|
Pregnancy period (days) | 18 – 21 | 21 – 23 | 110 – 118 |
Placenta type | Discoidal, decidual hemoendothelial choroidea |
Discoidal, decidual hemoendothelial choroidea |
Epitheliochorial |
Litter size | 6 – 12 | 6 – 15 | 11 – 16 |
Birth weight (g) | 0.5 – 1.5 | 3 – 5 | 900 – 1600 |
Weaning weight male/female (g) | 18 – 25/16 – 25 | 55 – 90/45 – 80 | 6000 – 8000 |
Suckling period (days) | 21–28 | 21 | 28–49 |
Solid diet beginning (days) | 10 | 12 | 12 – 15 |
Puberty male/female (week) | 4 – 6/5 | 6/6 – 8 | 20 – 28 |
Life expectancy (years) | 1 - 2 | 2 - 3 | 14 – 18 |
Table data - Otis and Brent (1954)[29] Links: timeline |
Respiratory Development
Respiratory Stages - Species Comparison - Stages Gestational age (days) | |||||
---|---|---|---|---|---|
Species | Term | Embryonic | Pseudoglandular | Canalicular | Saccular |
human | 280 | < 42 | 52 - 112 | 112 - 168 | 168 |
primate | 168 | < 42 | 57 - 80 | 80 - 140 | 140 |
sheep | 150 | < 40 | 40 - 80 | 80 - 120 | 120 |
rabbit | 32 | < 18 | 21 - 24 | 24 - 27 | 27 |
rat | 22 | < 13 | 16 - 19 | 19 - 20 | 21 |
mouse | 20 | < 9 | 16 | 18 | 19 |
Data modified from[30]
Links: respiratory | Respiratory Comparison | Mouse Human Respiratory | Mouse respiratory stages | mouse | rat | rabbit | Timeline Comparisons |
Timed Pregnancy
- Presence of the vaginal plug indicates that the mating occurred.
- Assumes that fertilization takes place around midnight during a 7pm to 5am dark cycle.
- Check for vaginal plugs early in the morning, because they fall out or are no longer detectable ~12 hours or sooner after mating.
- Noon of the day on which the vaginal plug is found the embryos are aged "0.5 dpc" (days post coitum).
- Noon on the next day, the embryos are 1.5 dpc, and so on.
References
- ↑ 1.0 1.1 Theiler K. The House Mouse: Atlas of Mouse Development (1972, 1989) Springer-Verlag, NY. Online
- ↑ 2.0 2.1 Downs KM & Davies T. (1993). Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope. Development , 118, 1255-66. PMID: 8269852
- ↑ Williams BS & Doyle MD. (1996). An Internet atlas of mouse development. Comput Med Imaging Graph , 20, 433-47. PMID: 9007211
- ↑ Wong MD, van Eede MC, Spring S, Jevtic S, Boughner JC, Lerch JP & Henkelman RM. (2015). 4D atlas of the mouse embryo for precise morphological staging. Development , 142, 3583-91. PMID: 26487781 DOI.
- ↑ Geyer SH, Reissig L, Rose J, Wilson R, Prin F, Szumska D, Ramirez-Solis R, Tudor C, White J, Mohun TJ & Weninger WJ. (2017). A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5). J. Anat. , 230, 710-719. PMID: 28185240 DOI.
- ↑ Lu CC & Robertson EJ. (2004). Multiple roles for Nodal in the epiblast of the mouse embryo in the establishment of anterior-posterior patterning. Dev. Biol. , 273, 149-59. PMID: 15302604 DOI.
- ↑ <pubmed>9165112</pubmed>
- ↑ 8.0 8.1 Cao L, Shitara H, Sugimoto M, Hayashi J, Abe K & Yonekawa H. (2009). New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. PLoS Genet. , 5, e1000756. PMID: 19997484 DOI.
- ↑ 9.0 9.1 Buckingham M, Meilhac S & Zaffran S. (2005). Building the mammalian heart from two sources of myocardial cells. Nat. Rev. Genet. , 6, 826-35. PMID: 16304598 DOI.
- ↑ 10.0 10.1 Mort RL, Hay L & Jackson IJ. (2010). Ex vivo live imaging of melanoblast migration in embryonic mouse skin. Pigment Cell Melanoma Res , 23, 299-301. PMID: 20067551 DOI.
- ↑ 11.0 11.1 11.2 11.3 11.4 Taher L, Collette NM, Murugesh D, Maxwell E, Ovcharenko I & Loots GG. (2011). Global gene expression analysis of murine limb development. PLoS ONE , 6, e28358. PMID: 22174793 DOI.
- ↑ 12.0 12.1 12.2 12.3 12.4 12.5 Ronca AE, Fritzsch B, Bruce LL & Alberts JR. (2008). Orbital spaceflight during pregnancy shapes function of mammalian vestibular system. Behav. Neurosci. , 122, 224-32. PMID: 18298265 DOI.
- ↑ 13.0 13.1 Matsuyama M, Aizawa S & Shimono A. (2009). Sfrp controls apicobasal polarity and oriented cell division in developing gut epithelium. PLoS Genet. , 5, e1000427. PMID: 19300477 DOI.
- ↑ Jiang X, Rowitch DH, Soriano P, McMahon AP & Sucov HM. (2000). Fate of the mammalian cardiac neural crest. Development , 127, 1607-16. PMID: 10725237
- ↑ Little MH, Brennan J, Georgas K, Davies JA, Davidson DR, Baldock RA, Beverdam A, Bertram JF, Capel B, Chiu HS, Clements D, Cullen-McEwen L, Fleming J, Gilbert T, Herzlinger D, Houghton D, Kaufman MH, Kleymenova E, Koopman PA, Lewis AG, McMahon AP, Mendelsohn CL, Mitchell EK, Rumballe BA, Sweeney DE, Valerius MT, Yamada G, Yang Y & Yu J. (2007). A high-resolution anatomical ontology of the developing murine genitourinary tract. Gene Expr. Patterns , 7, 680-99. PMID: 17452023 DOI.
- ↑ Wang Q, Zhao N, Kennard S & Lilly B. (2012). Notch2 and Notch3 function together to regulate vascular smooth muscle development. PLoS ONE , 7, e37365. PMID: 22615991 DOI.
- ↑ 17.0 17.1 17.2 Munger SC, Natarajan A, Looger LL, Ohler U & Capel B. (2013). Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination. PLoS Genet. , 9, e1003630. PMID: 23874228 DOI.
- ↑ Anderson RH, Webb S, Brown NA, Lamers W & Moorman A. (2003). Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart , 89, 1110-8. PMID: 12923046
- ↑ 19.0 19.1 Karl J & Capel B. (1998). Sertoli cells of the mouse testis originate from the coelomic epithelium. Dev. Biol. , 203, 323-33. PMID: 9808783 DOI.
- ↑ Taylor E, Taoudi S & Medvinsky A. (2010). Hematopoietic stem cell activity in the aorta-gonad-mesonephros region enhances after mid-day 11 of mouse development. Int. J. Dev. Biol. , 54, 1055-60. PMID: 20711982 DOI.
- ↑ 21.0 21.1 21.2 21.3 21.4 Savolainen SM, Foley JF & Elmore SA. (2009). Histology atlas of the developing mouse heart with emphasis on E11.5 to E18.5. Toxicol Pathol , 37, 395-414. PMID: 19359541 DOI.
- ↑ Nicholas CR, Haston KM & Pera RA. (2010). Intact fetal ovarian cord formation promotes mouse oocyte survival and development. BMC Dev. Biol. , 10, 2. PMID: 20064216 DOI.
- ↑ Savolainen SM, Foley JF & Elmore SA. (2009). Histology atlas of the developing mouse heart with emphasis on E11.5 to E18.5. Toxicol Pathol , 37, 395-414. PMID: 19359541 DOI.
- ↑ Ozaki T, Nagashima K, Kusakabe T, Kakudo K & Kimura S. (2011). Development of thyroid gland and ultimobranchial body cyst is independent of p63. Lab. Invest. , 91, 138-46. PMID: 20697379 DOI.
- ↑ Vondenhoff MF, van de Pavert SA, Dillard ME, Greuter M, Goverse G, Oliver G & Mebius RE. (2009). Lymph sacs are not required for the initiation of lymph node formation. Development , 136, 29-34. PMID: 19060331 DOI.
- ↑ 26.0 26.1 Robinson GW. (2007). Cooperation of signalling pathways in embryonic mammary gland development. Nat. Rev. Genet. , 8, 963-72. PMID: 18007652 DOI.
- ↑ Chorro L, Sarde A, Li M, Woollard KJ, Chambon P, Malissen B, Kissenpfennig A, Barbaroux JB, Groves R & Geissmann F. (2009). Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J. Exp. Med. , 206, 3089-100. PMID: 19995948 DOI.
- ↑ Shelton DN, Fornalik H, Neff T, Park SY, Bender D, et al. (2012) The Role of LEF1 in Endometrial Gland Formation and Carcinogenesis. PLoS ONE 7(7): e40312. doi:10.1371/journal.pone.0040312
- ↑ Otis EM and Brent R. Equivalent ages in mouse and human embryos. (1954) Anat Rec. 120(1):33-63. PMID 13207763
- ↑ Pinkerton KE & Joad JP. (2000). The mammalian respiratory system and critical windows of exposure for children's health. Environ. Health Perspect. , 108 Suppl 3, 457-62. PMID: 10852845
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Cite this page: Hill, M.A. (2024, May 25) Embryology Mouse Timeline Detailed. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Timeline_Detailed
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