Mouse Development

From Embryology
Mouse.jpg

Introduction

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. While being an ideal model organism, only a relatively small amount (1.5%) of the total mouse genome has been sequenced. 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 | original page

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

Some Recent Findings

Mouse E14.5 from transcriptome atlas[2]
  • A conditional knockout resource for the genome-wide study of mouse gene function[3] "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."

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
Mouse 1 cell Mouse 2 cell Mouse morula Mouse early blastocyst Mouse hatched blastocyst


Early mouse development cartoon.jpg

Early mouse development model[4]


Mouse inner cell mass cell types 01.jpg Model embryo to 128 cell stage icon.jpg
Live cell imaging and tracking[5]
  • (A) GFP-GPI expression from E.2.5 to E4.5. Deconvolved fluorescence and differential interference contrast time-lapse images overlaid with Simi BioCell cell-tracking spheres.
  • (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. A cell was defined as occupying an inside position by the orientation of the cell division that generated it, by its enclosure from the outside environment by neighboring cells, and by continued analysis of its position as development progressed. Allocation to trophectoderm (TE), EPI, or PE and apoptosis (A) are indicated.


Simulation of Zygote to Blastocyst[4]
  • 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.


Links: Quicktime | Quicktime version | Flash version


Links: Mouse Stages

Later Mouse Development

Links: Mouse Stages | Mouse Timeline Detailed

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.

Spermatozoa Development

Mouse spermatogonial self-renewal[9]

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

Neural Development

The data below is summarised from a study of early neural development in the mouse.[10]

  • 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.[11] [12]

Urogenital Development

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.[13]

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

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 chart shows the origins and relationships of inbred mouse strains. The chart is available as a PDF document [../pdf/mouse_genealogy.pdf Locally] or from JAX Labs and was originally published by Beck etal., 2000.

Mouse Genome

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

  1. The House Mouse: Atlas of Mouse Development by Theiler Springer-Verlag, NY (1972, 1989). | online book
  2. 2.0 2.1 <pubmed>21267068</pubmed>| PLoS Biol. | Eurexpress transcriptome atlas
  3. <pubmed>21677750</pubmed>
  4. 4.0 4.1 <pubmed>21573197</pubmed>| PMC3088645 | PLoS Comput Biol.
  5. <pubmed>20308546</pubmed>| PMC2852013 | PNAS
  6. <pubmed>20704721</pubmed>| BMC Dev Biol.
  7. 7.0 7.1 7.2 7.3 7.4 <pubmed>16683035</pubmed>| PLoS Genetics
  8. <pubmed>18713865</pubmed>| PNAS
  9. Zhou Q, Griswold MD. Regulation of spermatogonia. StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute. PMID20614596 | http://www.ncbi.nlm.nih.gov/books/NBK27035/ Bookshelf]
  10. Neurulation in the mouse: manner and timing of neural tube closure. Sakai Y. Anat Rec. 1989 Feb;223(2):194-203. PMID: 2712345
  11. The histogenetic potential of neural plate cells of early-somite-stage mouse embryos. Chan WY, Tam PP. J Embryol Exp Morphol. 1986 Jul;96:183-93. PMID: 3805982
  12. Neurulation in the mouse. I. The ontogenesis of neural segments and the determination of topographical regions in a central nervous system. Sakai Y. Anat Rec. 1987 Aug;218(4):450-7. PMID: 3662046
  13. <pubmed>17452023</pubmed>| PMC2117077

Search Pubmed

Search Pubmed: Mouse Development | Mouse Embryology

Additional Images

Movies

Fertilization 001 icon.jpg Parental genome mix 01 icon.jpg Nodal-cilia-001-icon.jpg Somitogenesis 01 icon.jpg
Fertilization
mouse
Parental genome
mouse
Nodal cilia rotation
mouse
Somitogenesis
mouse
Primordial germ cell 001 icon.jpg Primordial germ cell 002 icon.jpg Primordial germ cell 003 icon.jpg Mouse CT E11.5 movie-icon.jpg
Migration 1 Migration 2 Migration 3 microCT E11.5

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

Mouse Embryology

Mouse Gene Expression

  • EMAGE is a database of in situ gene expression data in the mouse embryo and an accompanying suite of tools to search and analyse the data. (All site content, except where otherwise noted, is licensed under a Creative Commons Attribution License.)
  • Eurexpress transcriptome atlas a High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo.
  • GenePaint.org is a digital atlas of gene expression patterns in the mouse.

Mouse Genome

Mouse Jackson Laboratory

Mouse Diseases

Mouse Transgenics

Mouse Transgenic Facilities

Mouse Urogenital

Mouse Unsorted Links


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Cite this page: Hill, M.A. (2024, March 28) Embryology Mouse Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Development

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