Mouse Stages

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Introduction

Mouse.jpg

Theiler Stages divide mouse development into 26 prenatal and 2 postnatal stages and is based upon the publication The House Mouse: Atlas of Mouse Development by Theiler Springer-Verlag, NY (1972, 1989). There is also a newer 1993 Downs and Davies staging of the mouse embryo included in each Theiler stage (Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope.[1]

mouse

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


Species Embryonic Comparison Timeline
Carnegie Stage
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Table References  
Human

O'Rahilly R. (1979). Early human development and the chief sources of information on staged human embryos. Eur. J. Obstet. Gynecol. Reprod. Biol. , 9, 273-80. PMID: 400868
Otis EM and Brent R. Equivalent ages in mouse and human embryos. (1954) Anat Rec. 120(1):33-63. PMID 13207763

Mouse
Theiler K. The House Mouse: Atlas of Mouse Development (1972, 1989) Springer-Verlag, NY. Online
OTIS EM & BRENT R. (1954). Equivalent ages in mouse and human embryos. Anat. Rec. , 120, 33-63. PMID: 13207763

Rat
Witschi E. Rat Development. In: Growth Including Reproduction and Morphological Development. (1962) Altman PL. and Dittmer DS. ed. Fed. Am. Soc. Exp. Biol., Washington DC, pp. 304-314.
Pérez-Cano FJ, Franch À, Castellote C & Castell M. (2012). The suckling rat as a model for immunonutrition studies in early life. Clin. Dev. Immunol. , 2012, 537310. PMID: 22899949 DOI.

Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | Medaka | Category:Timeline

Theiler Stage 1

  • Zygote
  • One-cell stage embryo (fertilised egg)
  • 1 cell. Zona pellucida present.
  • 0-0.9 dpc (range 0-2.5 dpc)

Theiler Stage 2

  • Blastomeres
  • 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 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)    

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)

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)
  • Equivalent Witschi Stage in rat = 8
  • Equivalent Carnegie Stage in human = 4

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)
  • Equivalent Witschi Stage in rat = 10
  • Equivalent Carnegie Stage in human = 5

Theiler Stage 8

  • 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)
  • Equivalent Witschi Stage in rat = 10-11
  • Equivalent Carnegie Stage in human = 5

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)
  • == 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)
  • Equivalent Downs and Davies stages: MS - LS (mid-streak to late streak)
  • Equivalent Witschi Stage in rat = 12
  • Equivalent Carnegie Stage in humans = 8
  • 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)
  • Equivalent Witschi Stage in rat = 12
  • Equivalent Carnegie Stage in humans = 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)
  • Equivalent Witschi Stage in rat = 12-13
  • Equivalent Carnegie Stage in humans = 9
  • 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)
  • Equivalent Witschi Stage in rat = 12-13
  • Equivalent Carnegie Stage in humans = 9
  • 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)
  • Equivalent Witschi Stage in rat = 12-13.
  • Equivalent Carnegie Stage in humans = 9
  • 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)
  • Equivalent Witschi Stage in rat = 12-13
  • Equivalent Carnegie Stage in humans = 9
  • == 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
  • Equivalent Witschi Stage in rat = 14-15
  • Equivalent Carnegie Stage in humans = 9
  • 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 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
  • Equivalent Witschi Stage in rat = 14-15
  • Equivalent Carnegie Stage in humans = 9
  • == 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.
  • Notochord and dorsal prepancreatic endoderms remain in contact until about the 13-somite stage.
  • Absent: 3rd branchial arch.
  • Embryonic age = 8.5 dpc (range 8-9.25 dpc)
  • 8-12 somite pairs
  • Equivalent Witschi Stage in rat = 15
  • Equivalent Carnegie Stage in humans = 10
  • == Theiler Stage 14 ==

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.
  • 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
  • Equivalent Witschi Stage in rat = 16
  • Equivalent Carnegie Stage in humans = 11
  • == Theiler Stage 15 ==
Mouse E9.5

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.
  • Lung development begins.
  • Pancreas first indication of morphogenesis, dorsal pancreatic bud (22-25 somites).
  • Absent: hindlimb bud, Rathke's pouch.
  • Embryonic age = 9.5 dpc (range 9-10.25 dpc)
  • 21-29 somite pairs
  • Equivalent Witschi Stage in rat = 17-19
  • Equivalent Carnegie Stage in humans = 12

Theiler Stage 16

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.
  • Pancreas ventral pancreatic bud appears (30 somites, 10.25-10.5).
  • Absent: thin and long tail.
  • Embryonic age = 10 dpc (range 9.5-10.75 dpc)
  • 30-34 somite pairs
  • Equivalent Witschi Stage in rat = 20-21
  • Equivalent Carnegie Stage in humans = 13-15
  • == Theiler Stage 17 ==
Mouse E10.5

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
  • Equivalent Witschi Stage in rat = 24-25
  • Equivalent Carnegie Stage in humans = 13-15

Theiler Stage 18

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.
  • The nasal pits start to form. Absent: auditory hillocks, anterior footplate.
  • Embryonic age = 11 dpc (range 10.5-11.25 dpc)
  • 40-44 somite pairs
  • Equivalent Witschi Stage in rat = 25-26
  • Equivalent Carnegie Stage in humans = 13-15

Theiler Stage 19

Mouse E11.5
Mouse E11.5

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
  • Equivalent Witschi Stage in rat = 26-27
  • Equivalent Carnegie Stage in humans = 16

Theiler Stage 20

Mouse CT E12.5
Mouse E12.5

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
  • Equivalent Witschi Stage in rat = 28
  • Equivalent Carnegie Stage in humans = 17

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
  • Equivalent Witschi Stage in rat = 29-30
  • Equivalent Carnegie Stage in humans = 18-19
  • == Theiler Stage 22 ==
Mouse CT E14.5

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
  • Equivalent Witschi Stage in rat = 31
  • Equivalent Carnegie Stage in humans = 20-23

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
  • Equivalent Witschi Stage in rat = 32
  • Human fetal period.

Theiler Stage 24

Mouse CT E16.5

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
  • Equivalent Witschi Stage in rat = 33   

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
  • Equivalent Witschi Stage in rat = 34   
  • == Theiler Stage 26 ==
Mouse CT E18.5

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
  • Equivalent Witschi Stage in rat = 35

Theiler Stage 27

  • New born Mouse

Theiler Stage 28

  • Post-natal development

Data

CT Images

  • Virtual histology of transgenic mouse embryos for high-throughput phenotyping. Johnson JT, Hansen MS, Wu I, Healy LJ, Johnson CR, Jones GM, Capecchi MR, Keller C. PLoS Genet. 2006 Apr;2(4):e61. Epub 2006 Apr 28. PMID: 16683035
  • High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database. Petiet AE, Kaufman MH, Goddeeris MM, Brandenburg J, Elmore SA, Johnson GA. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12331-6. Epub 2008 Aug 19. PMID: 18713865 | PNAS

Species Stages Comparison

The table below gives an approximate comparison of human, mouse and rat embryos based upon Carnegie staging.

Species Embryonic Comparison Timeline
Carnegie Stage
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Table References  
Human

O'Rahilly R. (1979). Early human development and the chief sources of information on staged human embryos. Eur. J. Obstet. Gynecol. Reprod. Biol. , 9, 273-80. PMID: 400868
Otis EM and Brent R. Equivalent ages in mouse and human embryos. (1954) Anat Rec. 120(1):33-63. PMID 13207763

Mouse
Theiler K. The House Mouse: Atlas of Mouse Development (1972, 1989) Springer-Verlag, NY. Online
OTIS EM & BRENT R. (1954). Equivalent ages in mouse and human embryos. Anat. Rec. , 120, 33-63. PMID: 13207763

Rat
Witschi E. Rat Development. In: Growth Including Reproduction and Morphological Development. (1962) Altman PL. and Dittmer DS. ed. Fed. Am. Soc. Exp. Biol., Washington DC, pp. 304-314.
Pérez-Cano FJ, Franch À, Castellote C & Castell M. (2012). The suckling rat as a model for immunonutrition studies in early life. Clin. Dev. Immunol. , 2012, 537310. PMID: 22899949 DOI.

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. <pubmed>8269852</pubmed>
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Cite this page: Hill, M.A. (2024, March 28) Embryology Mouse Stages. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Stages

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