Mouse Development

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Introduction

Mouse.jpg
Mouse E0-E5.jpg

The mouse (taxon-mus) has always been a good embryological model, generating easily (litters 8-20) and quickly (21d). Mouse embryology really expanded when molecular biologists used mice for gene knockouts. Suddenly it was necessary to understand development in order to understand the effect of knocking out the gene.


There are over 450 different strains of inbred research mice, and these strains have recently been organized into a chart. Those interested in the mouse reproductive cycle should also look at the mouse estrous cycle.


There are several systems for staging mouse development. The original and most widely used is the Theiler Stages system, which divides mouse development into 26 prenatal and 2 postnatal stages.[1]


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
Mouse Movies 
Mouse Zygote  
Fertilization 001 icon.jpg
 ‎‎Mouse Fertilisation
Page | Play
Mouse zygote division icon.jpg
 ‎‎Zygote Mitosis
Page | Play
Mouse zygote division 02 icon.jpg
 ‎‎Early Division
Page | Play
Parental genome mix 01 icon.jpg
 ‎‎Parental Genomes
Page | Play
Mouse blastocyst movie icon.jpg
 ‎‎Mouse Blastocyst
Page | Play
Mouse Various  
Oocyte Meiosis 01 icon.jpg
 ‎‎Oocyte Meiosis
Page | Play
DNA bead-induced ectopic polar body-icon.jpg
 ‎‎Ectopic Polar Body
Page | Play
Mouse spermatozoa mito movie icon.jpg
 ‎‎Male Mitochondria
Page | Play
Mouse spermatozoa mito movie icon.jpg
 ‎‎Male Mitochondria
Page | Play
Mouse Blastocyst Cdx2 icon.jpg
 ‎‎Blastocyst Cdx2
Page | Play
Model embryo to 128 cell stage icon.jpg
 ‎‎Blastocyst Model
Page | Play
Mouse lipid droplets icon.jpg
‎‎Mouse Lipid Drops
Page | Play
Somitogenesis 01 icon.jpg
 ‎‎Somitogenesis
Page | Play
Mouse-melanoblast migration icon.jpg
 ‎‎Mouse Melanoblast
Page | Play
Mouse limb gene expression icon.jpg
 ‎‎Limb Genes
Page | Play
Mouse microCT  
Mouse CT E11.5 movie-icon.jpg
 ‎‎Mouse E11.5 CT
Page | Play
Mouse CT E12.5 sagittal movie.jpg
 ‎‎Mouse E12.5 CT
Page | Play
Mouse CT E12.5 coronal movie.jpg
 ‎‎Mouse E12.5 CT
Page | Play
Mouse CT E12.5 axial movie.jpg
 ‎‎Mouse E12.5 Axial
Page | Play
Mouse embryo E13 microCT icon.jpg
 ‎‎Mouse E13 microCT
Page | Play
Mouse embryo E14 microCT icon.jpg
 ‎‎Mouse E14 microCT
Page | Play
Mouse embryo E14 sectioned microCT icon.jpg
 ‎‎Mouse E14 microCT
Page | Play
Mouse embryo E15 microCT icon.jpg
 ‎‎Mouse E15 microCT
Play | Play
Mouse face microCT icon.jpg
 ‎‎Mouse Face
Page | Play
Mouse-Cephalic-plexus-11somite 01.jpg
 ‎‎Mouse Head Plexus
Page | Play
Historic Embryology - Mouse 
1927 Growth | 1927a Gonads 1 | 1927b Gonads 2 | 1928 Gonads 3 | 1932 Gonads 4 | 1962 Oocyte | 2016 Heart


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 | E18.5 | 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

Some Recent Findings

Mouse E14.5 from transcriptome atlas[2]
  • In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level[3] "A light-sheet microscopy approach and computational platform that accommodates the dynamics of post-implantation development to reconstruct at single-cell resolution mouse embryogenesis from gastrulation to early organogenesis." YouTube

  • Conserved and Divergent Features of Human and Mouse Kidney Organogenesis[4] "Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day E15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies." renal
  • Histology Atlas of the Developing Prenatal and Postnatal Mouse Central Nervous System, with Emphasis on Prenatal Days E7.5 to E18.5[5] "By providing a well-illustrated overview summarizing major events of normal in utero and perinatal mouse CNS development with examples of common developmental abnormalities, this annotated, color atlas can be used to identify normal structure and histology when phenotyping genetically engineered mice and will enhance efforts to describe and interpret brain and spinal cord malformations as causes of mouse embryonic and perinatal lethal phenotypes. The schematics and images in this atlas illustrate major developmental events during gestation from embryonic day (E)7.5 to E18.5 and after birth from postnatal day (P)1 to P21." (More? See other mouse atlases by these authors: liver[6][7], heart[8]}
More recent papers  
Mark Hill.jpg
PubMed logo.gif

This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Mouse Development

Ziqi Chen, Fang Liu, Nanxin Zheng, Meng Guo, Leilei Bao, Yangyang Zhan, Mingjian Zhang, Yuanyu Zhao, Wenyuan Guo, Guoshan Ding Wuzhi capsule (Schisandra Sphenanthera extract) attenuates liver steatosis and inflammation during non-alcoholic fatty liver disease development. Biomed. Pharmacother.: 2018, 110;285-293 PubMed 30522014

Zhuo Wang, Ming Yan, Jia'an Li, Jiafu Long, Yan Li, Hongmin Zhang Dual functions of STAT3 in LPS-induced angiogenesis of hepatocellular carcinoma. Biochim Biophys Acta Mol Cell Res: 2018; PubMed 30521872

Peyman Avakh Majelan, Mehdi Mahdavi, Mohammad Hossein Yazdi, Elaheh Salimi, Mohammad Reza Pourmand Recombinant Staphylococcal Antigen-F (r-ScaF), a novel vaccine candidate against methicillin resistant Staphylococcus aureus infection: Potency and efficacy studies. Microb. Pathog.: 2018; PubMed 30521844

Liudmila Mus, Francesca Siani, Claudio Giuliano, Christina Ghezzi, Silvia Cerri, Fabio Blandini Development and biochemical characterization of a mouse model of Parkinson's disease bearing defective glucocerebrosidase activity. Neurobiol. Dis.: 2018; PubMed 30521842

W Joseph Evans, Brett L Hurst, Christopher J Peterson, Arnaud J Van Wettere, Craig W Day, Donald F Smee, E Bart Tarbet Development of a respiratory disease model for enterovirus D68 in 4-week-Old mice for evaluation of antiviral therapies. Antiviral Res.: 2018; PubMed 30521834

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development[9] "Correct neuronal migration is crucial for brain architecture and function. During cerebral cortex development (corticogenesis), excitatory neurons generated in the proliferative zone of the dorsal telencephalon (mainly ventricular zone) move through the intermediate zone and migrate past the neurons previously located in the cortical plate and come to rest just beneath the marginal zone. The in utero electroporation technique is a powerful method for rapid gain- and loss-of-function studies of neuronal development, especially neuronal migration."
  • Cell fate decisions and axis determination in the early mouse embryo[10] "The early cell fate decisions lead to the generation of three lineages in the pre-implantation embryo: the epiblast, the primitive endoderm and the trophectoderm. Shortly after implantation, the anterior-posterior axis is firmly established. ... In this review, we address the timing of the first cell fate decisions and of the establishment of embryonic polarity, and we ask how far back one can trace their origins."
  • A conditional knockout resource for the genome-wide study of mouse gene function[11] "Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome."
  • A high-resolution anatomical atlas of the transcriptome in the mouse embryo[2] "We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures."

Movies

The collapsible tables below contain a number of movies showing aspects of mouse development.

Mouse Zygote  
Fertilization 001 icon.jpg
 ‎‎Mouse Fertilisation
Page | Play
Mouse zygote division icon.jpg
 ‎‎Zygote Mitosis
Page | Play
Mouse zygote division 02 icon.jpg
 ‎‎Early Division
Page | Play
Parental genome mix 01 icon.jpg
 ‎‎Parental Genomes
Page | Play
Mouse blastocyst movie icon.jpg
 ‎‎Mouse Blastocyst
Page | Play
Mouse Various  
Oocyte Meiosis 01 icon.jpg
 ‎‎Oocyte Meiosis
Page | Play
DNA bead-induced ectopic polar body-icon.jpg
 ‎‎Ectopic Polar Body
Page | Play
Mouse spermatozoa mito movie icon.jpg
 ‎‎Male Mitochondria
Page | Play
Mouse spermatozoa mito movie icon.jpg
 ‎‎Male Mitochondria
Page | Play
Mouse Blastocyst Cdx2 icon.jpg
 ‎‎Blastocyst Cdx2
Page | Play
Model embryo to 128 cell stage icon.jpg
 ‎‎Blastocyst Model
Page | Play
Mouse lipid droplets icon.jpg
‎‎Mouse Lipid Drops
Page | Play
Somitogenesis 01 icon.jpg
 ‎‎Somitogenesis
Page | Play
Mouse-melanoblast migration icon.jpg
 ‎‎Mouse Melanoblast
Page | Play
Mouse limb gene expression icon.jpg
 ‎‎Limb Genes
Page | Play
Mouse microCT  
Mouse CT E11.5 movie-icon.jpg
 ‎‎Mouse E11.5 CT
Page | Play
Mouse CT E12.5 sagittal movie.jpg
 ‎‎Mouse E12.5 CT
Page | Play
Mouse CT E12.5 coronal movie.jpg
 ‎‎Mouse E12.5 CT
Page | Play
Mouse CT E12.5 axial movie.jpg
 ‎‎Mouse E12.5 Axial
Page | Play
Mouse embryo E13 microCT icon.jpg
 ‎‎Mouse E13 microCT
Page | Play
Mouse embryo E14 microCT icon.jpg
 ‎‎Mouse E14 microCT
Page | Play
Mouse embryo E14 sectioned microCT icon.jpg
 ‎‎Mouse E14 microCT
Page | Play
Mouse embryo E15 microCT icon.jpg
 ‎‎Mouse E15 microCT
Play | Play
Mouse face microCT icon.jpg
 ‎‎Mouse Face
Page | Play
Mouse-Cephalic-plexus-11somite 01.jpg
 ‎‎Mouse Head Plexus
Page | Play
Links: Movies

Animal Model Comparison

Animal 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)[12]   Links: timeline

Oocyte Development

Mouse oogenesis [13]

Mouse oogenesis 02.jpg


Follicle size graph Oocyte size graph

Graphs show mouse and other species (Human, Pig, Hamster) comparison in follicle and oocyte size growth.[14] (See also Follicle size graph)


Links: Oocyte | Ovary

Early Mouse Development

Mouse E0-E5.jpg

Mouse-1 cell 01.jpg Mouse-2 cell 01.jpg Mouse-morula 01.jpg Mouse-early blastocyst 01.jpg Mouse-early blastocyst 02.jpg
zygote blastomeres morula early blastocyst hatched blastocyst


Early mouse development cartoon.jpg

Early mouse development model[15]


Mouse inner cell mass cell types 01.jpg Model embryo to 128 cell stage icon.jpg
Live cell imaging and tracking[16]
  • (A) GFP-GPI expression from E.2.5 to E4.5. Deconvolved fluorescence and differential interference contrast time-lapse images.
  • (B) Embryos stained to reveal Gata4-positive cells adjacent to mature blastocyst cavity confirming normal development during each imaging session. Gata4-positive cells were present in a one-cell-thick surface layer.
  • (C) Lineage tree from representative embryo. All cells were traced to the early 32-cell blastocyst; then inside cells were traced to late blastocyst. Allocation to trophectoderm (TE), EPI, or PE and apoptosis (A) are indicated.
Simulation of Zygote to Blastocyst[15]
  • An example of a complete simulation of embryo development from 1 to 128 cells.
  • Simulation includes trophectoderm formation in “position-based” model, blastocoel growth and endoderm formation by differential adhesion and directional signal mechanisms.
  • Note - cell colour coding is different from adjacent live imaging study.
Model embryo to 32 cell stage icon.jpg
 ‎‎Morula Model
Page | Play
Model embryo to 128 cell stage icon.jpg
 ‎‎Blastocyst Model
Page | Play


Mouse zygote protein expression


Links: Mouse Stages

Later Mouse Development

Links: Mouse Stages | Mouse Timeline Detailed

Mouse Limb


Links: Limb Development

Carnegie 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.

Placenta Development

Maternal

  • Uterine radial artery branches into 5-10 dilated spiral arteries.[17]
  • Spiral arteries then converge at the trophoblast giant cell layer and empty into straight trophoblast-lined "canals".

Embryonic

  • Embryonic placenta originates from the ectoplacental cone and the extra-embryonic ectoderm.
  • endothelial cells derive from the allantois.
  • embryonic day (E 10) - placenta divided into three layers associated with maternal decidual cells.
  1. Labyrinth - (equivalent to human villi) a selective barrier on the fetal side, is an array of fetal and maternal vessels.
  2. Junctional zone - (spongy layer) produce hormones and contains numerous cavities. The trophoblast cells form spongiotrophoblasts and the glycogen cells, that later (E 12.5) migrate into the maternal decidua.
  3. Giant cells - next to the uterine cells form the outermost fetal cell layer until (E 12).
Mouse Placenta Vasculature (E16.5)
Mouse placenta 01.jpg Mouse placenta 02.jpg


  • Arterial side - blue resin.
  • Venous side - red resin.
superior view (maternal side) lateral view (maternal side at bottom)

Spermatozoa Development

Mouse spermatogonial self-renewalZhou Q & Griswold MD. (2008). Regulation of spermatogonia. , , . PMID: 20614596 DOI.

The process of spermatogenesis takes approximately 35 days:

  • mitotic phase (11 days)
  • meiotic phase (10 days)
  • post-meiotic phase (14 days)

Spermatogonial stem cells (SSCs)

The diploid germ cells, spermatogonial stem cells (SSCs), are located on the basement membrane of the seminiferous tubules

  • adult mouse testis about 30,000 SSCs
  • either divides into two new single cells
  • or into a pair of spermatogonia (Apr)
    • that do not complete cytokinesis and stay connected by an intercellular bridge

Primitive spermatogonia subset

  • Asingle (As, single isolated spermatogonia)
  • Apaired (Apr, interconnected spermatogonial pairs)
  • Aaligned (Aal, interconnected 4, 8, or 16 spermatogonia)
    • specifically termed Aal-4, Aal-8, and Aal-16

Primitive spermatogonia cells transform without cell division into more differentiating A1 spermatogonia that undergo 6 mitotic and 2 meiotic divisions to eventually form haploid spermatids.


Links: Spermatozoa Development | Testis Development

Limb Development

Mouse limb skeleton cartoon.jpg

Mouse limb skeleton cartoon[18]

Fore-limb and hind-limb buds for stages E9.5 to E13.5. Hindlimbs are morphologically delayed by about half a day.

  • Light blue - indicate mesenchymal condensations.
  • Thick black lines - indicate cartilage as determined by alcian blue staining.

Mouse limb tissue development.jpg

Change in cell types and tissue formation as a function of mouse developmental stage.[18]


Links: Limb Development

Neural Development

The data below is summarised from a study of early neural development in the mouse.[19]

  • initial fusion of apposing neural folds occurred at the level of the intermediate point between the third and fourth somites (caudal myelencephalon) both rostrally and caudally
  • second fusion - at the original rostral end of the neural plate (rostrodorsally).
  • third fusion - in the caudal diencephalon (rostrally and caudally)
    • followed by complete closure of the telencephalic neuropore at the midpoint of the telencephalic roof
    • then complete closure of the metencephalic neuropore at the rostral part of the metencephalic roof
  • fourth fusion - at the original caudal end of the neural plate (rostrally)
  • caudal neuropore completely closed at the level of the future 33rd somite

See also these 1980's papers: neural plate cells of early-somite-stage mouse embryos[20] and Neurulation in the mouse.[21]

Urogenital Development

Mouse gonad development timeline.jpg

Mouse E11.0 to E12.0 shows the critical transition in the gonad from a bipotential to sexually-differentiated state. Based upon 2013 transcriptome analysis.[22]

A high-resolution description of the developing murine genitourinary tract from Theiler stage (TS) 17 (E10.5) through to TS27 (E19.5) and then to postnatal day 3 was published in 2007.[23]

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with tools to facilitate research. They intend to develop:

  • a molecular atlas of gene expression for the developing organs of the GenitoUrinary (GU) tract
  • a high resolution molecular anatomy that highlights development of the GU system
  • mouse strains to facilitate developmental and functional studies within the GU system
  • tutorials describing GU organogenesis
  • rapid access to primary data via the GUDMAP database


Links: GUDMAP | GUDMAP - Renal Development | GUDMAP - Genital Development


Lung Development

Vertebrate lung development is generally divided into 5 stages, based upon growth and histological appearance. Mouse age data[24]

Stage Mouse Age Features
Embryonic E9 to E11.5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs
Pseudoglandular E11.5 to E16.5 conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching
Canalicular E16.5 to E17.5 bronchioles are produced, increasing number of capillaries in close contact with cuboidal epithelium and the beginning of alveolar epithelium development
Saccular E17.5 to PN5 alveolar ducts and air sacs are developed
Alveolar PN5 to PN28 secondary septation occurs, marked increase of the number and size of capillaries and alveoli
Links: Species Comparison | Mouse Human Comparison | Mouse respiratory stages | Respiratory Development

Human and Mouse Comparison

Stage Human Mouse Features
Embryonic week 4 to 5 E9 to E11.5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs
Pseudoglandular week 5 to 17 E11.5 to E16.5 conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching
Canalicular week 16 to 25 E16.5 to E17.5 bronchioles are produced, increasing number of capillaries in close contact with cuboidal epithelium and the beginning of alveolar epithelium development
Saccular week 24 to 40 E17.5 to PN5 alveolar ducts and air sacs are developed
Alveolar late fetal to 8 years PN5 to PN28 secondary septation occurs, marked increase of the number and size of capillaries and alveoli
Links: Species Comparison | Mouse Human Comparison | Mouse respiratory stages | Respiratory Development

Note that while human third trimester fetus has regular respiratory breathing movements, the common mouse model (C57BL/6J} completely lacks these movements.[25]


Respiratory Species Comparison

Mouse lung development[26]
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[27]   

Links: respiratory | Respiratory Comparison | Mouse Human Respiratory | Mouse respiratory stages | mouse | rat | rabbit | Timeline Comparisons


Bronchial Branching

The following images are from a recent study of the development of bronchial branching in he mouse between E10 to E14.[28]

Mesenchyme (red) and epithelium (blue) the study used knockout mice to show the role of Wnt signalling in branching morphogenesis.

Mouse respiratory 36 to 60 somites.jpg

Mouse respiratory 44 to 60 somites.jpg

Links: movie - 36-60 somites | Respiratory System Development | Wnt

Endocrine Development

Hypothalamic-Pituitary-Adrenal Axis

Two postnatal phases identified[29]:

  1. first phase - (pnd 1 (birth) to pnd 12) corresponds to the hypo-responsive period (SHRP) in the rat. Basal corticosterone levels were low and novelty exposure did not enhance corticosterone or ACTH levels. High expression of CRH in the paraventricular nucleus (PVN) of the hypothalamus. Expression levels of GR in the hippocampus and UCN3 in the perifornical area are low at birth but increase significantly during the SHRP, both reach maximum expression level at pnd 12.
  2. second phase - mice developed past the SHRP exhibit enhanced corticosterone basal levels and a response of ACTH and corticosterone to mild novelty stress. CRH expression was decreased significantly, expression of urocortin 3 (UCN3) and glucocorticoid receptor (GR) remained high, with a small decrease at pnd 16.

Mouse Knockouts

Knowledge about mouse development has rapidly expanded as it has become the model animal system for genetic "knock out " studies. This technology actually requires development of defined breeding programs, pseudo-pregnancy, in vitro fertilization, molecular biology, and good old fashioned histology. Without understanding normal development the molecular biologists don't stand a hope of understanding what their gene knock out has done. There is a database of all existing mouse knockouts and their consequences.

Murine Development Control Genes

Kessel, M. and Gruss, P. Science 249 374-379 (1990)

An early review of the genes, and method of identifying them, involved in early mouse development. In particular discusses Homeobox genes. (homeobox is 183bp encoding a 61 amino acid DNA-binding domain)

  • Gene families
    • Hox
    • Pax
    • POU

The Genealogy Chart of Inbred Strains

This Nature paper[30] chart shows the origins and relationships of inbred mouse strains. The chart is available as a PDF document [Media:Mouse_genealogy.pdf Locally] or from JAX Labs and was originally published by Beck etal., 2000.

  • Hairless mutant mouse - wave of hair loss in a rostral to caudal sequence starting at 3 weeks of age, first identified in the 1930's.

Mouse Genome

Normal Mouse Karyotype
Normal Mouse Karyotype

Mouse Genome completed December 2002, a draft sequence and analysis of the genome of the C57BL/6J mouse strain.

  • less than 30,000 genes
  • estimated size is 2.5 Gb, smaller than the human genome
  • about 40% of the human and mouse genomes can be directly aligned
  • about 80% of human genes have one corresponding gene in the mouse genome
Links: Mouse Genome Sequencing: Mus musculus | Mouse Genome Informatics | Mouse Genome Project | Nature - Mouse Genome

References

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  2. 2.0 2.1 Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I, Lin-Marq N, Koch M, Bilio M, Cantiello I, Verde R, De Masi C, Bianchi SA, Cicchini J, Perroud E, Mehmeti S, Dagand E, Schrinner S, Nürnberger A, Schmidt K, Metz K, Zwingmann C, Brieske N, Springer C, Hernandez AM, Herzog S, Grabbe F, Sieverding C, Fischer B, Schrader K, Brockmeyer M, Dettmer S, Helbig C, Alunni V, Battaini MA, Mura C, Henrichsen CN, Garcia-Lopez R, Echevarria D, Puelles E, Garcia-Calero E, Kruse S, Uhr M, Kauck C, Feng G, Milyaev N, Ong CK, Kumar L, Lam M, Semple CA, Gyenesei A, Mundlos S, Radelof U, Lehrach H, Sarmientos P, Reymond A, Davidson DR, Dollé P, Antonarakis SE, Yaspo ML, Martinez S, Baldock RA, Eichele G & Ballabio A. (2011). A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol. , 9, e1000582. PMID: 21267068 DOI.
  3. McDole K. etal., In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level DOI:https://doi.org/10.1016/j.cell.2018.09.031
  4. Lindström NO, McMahon JA, Guo J, Tran T, Guo Q, Rutledge E, Parvez RK, Saribekyan G, Schuler RE, Liao C, Kim AD, Abdelhalim A, Ruffins SW, Thornton ME, Baskin L, Grubbs B, Kesselman C & McMahon AP. (2018). Conserved and Divergent Features of Human and Mouse Kidney Organogenesis. J. Am. Soc. Nephrol. , 29, 785-805. PMID: 29449453 DOI.
  5. Chen VS, Morrison JP, Southwell MF, Foley JF, Bolon B & Elmore SA. (2017). Histology Atlas of the Developing Prenatal and Postnatal Mouse Central Nervous System, with Emphasis on Prenatal Days E7.5 to E18.5. Toxicol Pathol , 45, 705-744. PMID: 28891434 DOI.
  6. Crawford LW, Foley JF & Elmore SA. (2010). Histology atlas of the developing mouse hepatobiliary system with emphasis on embryonic days 9.5-18.5. Toxicol Pathol , 38, 872-906. PMID: 20805319 DOI.
  7. Swartley OM, Foley JF, Livingston DP, Cullen JM & Elmore SA. (2016). Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development. Toxicol Pathol , 44, 705-25. PMID: 26961180 DOI.
  8. 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.
  9. Nishimura YV, Shinoda T, Inaguma Y, Ito H & Nagata K. (2012). Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development. Med Mol Morphol , 45, 1-6. PMID: 22431177 DOI.
  10. Takaoka K & Hamada H. (2012). Cell fate decisions and axis determination in the early mouse embryo. Development , 139, 3-14. PMID: 22147950 DOI.
  11. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF & Bradley A. (2011). A conditional knockout resource for the genome-wide study of mouse gene function. Nature , 474, 337-42. PMID: 21677750 DOI.
  12. Otis EM and Brent R. Equivalent ages in mouse and human embryos. (1954) Anat Rec. 120(1):33-63. PMID 13207763
  13. Wang JJ, Ge W, Liu JC, Klinger FG, Dyce PW, De Felici M & Shen W. (2017). Complete in vitro oogenesis: retrospects and prospects. Cell Death Differ. , 24, 1845-1852. PMID: 28841213 DOI.
  14. Griffin J, Emery BR, Huang I, Peterson CM & Carrell DT. (2006). Comparative analysis of follicle morphology and oocyte diameter in four mammalian species (mouse, hamster, pig, and human). J. Exp. Clin. Assist. Reprod. , 3, 2. PMID: 16509981 DOI.
  15. 15.0 15.1 Krupinski P, Chickarmane V & Peterson C. (2011). Simulating the mammalian blastocyst--molecular and mechanical interactions pattern the embryo. PLoS Comput. Biol. , 7, e1001128. PMID: 21573197 DOI.
  16. Morris SA, Teo RT, Li H, Robson P, Glover DM & Zernicka-Goetz M. (2010). Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proc. Natl. Acad. Sci. U.S.A. , 107, 6364-9. PMID: 20308546 DOI.
  17. Adamson SL, Lu Y, Whiteley KJ, Holmyard D, Hemberger M, Pfarrer C & Cross JC. (2002). Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev. Biol. , 250, 358-73. PMID: 12376109
  18. 18.0 18.1 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.
  19. Sakai Y. (1989). Neurulation in the mouse: manner and timing of neural tube closure. Anat. Rec. , 223, 194-203. PMID: 2712345 DOI.
  20. Chan WY & Tam PP. (1986). The histogenetic potential of neural plate cells of early-somite-stage mouse embryos. J Embryol Exp Morphol , 96, 183-93. PMID: 3805982
  21. Sakai Y. (1987). Neurulation in the mouse. I. The ontogenesis of neural segments and the determination of topographical regions in a central nervous system. Anat. Rec. , 218, 450-7. PMID: 3662046 DOI.
  22. 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.
  23. 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.
  24. Maeda Y, Davé V & Whitsett JA. (2007). Transcriptional control of lung morphogenesis. Physiol. Rev. , 87, 219-44. PMID: 17237346 DOI.
  25. Kleven GA & Ronca AE. (2009). Prenatal behavior of the C57BL/6J mouse: a promising model for human fetal movement during early to mid-gestation. Dev Psychobiol , 51, 84-94. PMID: 18980217 DOI.
  26. Yu H, Wessels A, Chen J, Phelps AL, Oatis J, Tint GS & Patel SB. (2004). Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev. Biol. , 4, 1. PMID: 15005800 DOI.
  27. 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
  28. Kadzik RS, Cohen ED, Morley MP, Stewart KM, Lu MM & Morrisey EE. (2014). Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape. Proc. Natl. Acad. Sci. U.S.A. , 111, 12444-9. PMID: 25114215 DOI.
  29. Schmidt MV, Schmidt M, Enthoven L, van der Mark M, Levine S, de Kloet ER & Oitzl MS. (2003). The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int. J. Dev. Neurosci. , 21, 125-32. PMID: 12711350
  30. Beck JA, Lloyd S, Hafezparast M, Lennon-Pierce M, Eppig JT, Festing MF & Fisher EM. (2000). Genealogies of mouse inbred strains. Nat. Genet. , 24, 23-5. PMID: 10615122 DOI.


Reviews

Sutherland AE. (2016). Tissue morphodynamics shaping the early mouse embryo. Semin. Cell Dev. Biol. , 55, 89-98. PMID: 26820524 DOI.

Rossant J. (2016). Making the Mouse Blastocyst: Past, Present, and Future. Curr. Top. Dev. Biol. , 117, 275-88. PMID: 26969983 DOI.

Swartley OM, Foley JF, Livingston DP, Cullen JM & Elmore SA. (2016). Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development. Toxicol Pathol , 44, 705-25. PMID: 26961180 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.

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Cite this page: Hill, M.A. (2018, December 11) Embryology Mouse Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development

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