Mouse Development

From Embryology
Jump to: navigation, search

Contents

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 Knockout | Movie - Cephalic Plexus | ANAT2341 Project (2009) | Category:Mouse


Mouse Stages: E1 | E2.5 | E3 | E3.5 | E4.5 | E7.5 | 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 | E18.5 | E19 | E20 | Timeline | About timed pregnancy


Species 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 [2] 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 [1] Days 1 2 3 4 5 6 7 8 9.0 9.5 E10 10.5 11 11.5 12 12.5 13 13.5 E14 14.5 15 15.5 16
Rat [3] 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 that these Carnegie stages are only approximate day timings for average of embryos.
Links: Carnegie Stage Comparison


Some Recent Findings

Mouse E14.5 from transcriptome atlas[1]
  • Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development[2] "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[3] "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[4] "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[1] "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."

Animal Models

Postnatal Animal Models[5] 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

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[6]


Mouse inner cell mass cell types 01.jpg Model embryo to 128 cell stage icon.jpg
Live cell imaging and tracking[7]
  • (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[6]
  • 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


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 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 [2] 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 [1] Days 1 2 3 4 5 6 7 8 9.0 9.5 E10 10.5 11 11.5 12 12.5 13 13.5 E14 14.5 15 15.5 16
Rat [3] 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 that these Carnegie stages are only approximate day timings for average of embryos.
Links: Carnegie Stage Comparison

Placenta Development

  • 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-renewal[8]

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[9]

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.[9]


Links: Limb 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

Lung Development

Vertebrate lung development is generally divided into 5 stages, based upon growth and histological appearance. Mouse age data[14]

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

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
         


Endocrine Development

Hypothalamic-Pituitary-Adrenal Axis

Two postnatal phases identified[15]:

  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[16] 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.


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. 1.0 1.1 Graciana Diez-Roux, Sandro Banfi, Marc Sultan, Lars Geffers, Santosh Anand, David Rozado, Alon Magen, Elena Canidio, Massimiliano Pagani, Ivana Peluso, Nathalie Lin-Marq, Muriel Koch, Marchesa Bilio, Immacolata Cantiello, Roberta Verde, Cristian De Masi, Salvatore A Bianchi, Juliette Cicchini, Elodie Perroud, Shprese Mehmeti, Emilie Dagand, Sabine Schrinner, Asja Nürnberger, Katja Schmidt, Katja Metz, Christina Zwingmann, Norbert Brieske, Cindy Springer, Ana Martinez Hernandez, Sarah Herzog, Frauke Grabbe, Cornelia Sieverding, Barbara Fischer, Kathrin Schrader, Maren Brockmeyer, Sarah Dettmer, Christin Helbig, Violaine Alunni, Marie-Annick Battaini, Carole Mura, Charlotte N Henrichsen, Raquel Garcia-Lopez, Diego Echevarria, Eduardo Puelles, Elena Garcia-Calero, Stefan Kruse, Markus Uhr, Christine Kauck, Guangjie Feng, Nestor Milyaev, Chuang Kee Ong, Lalit Kumar, MeiSze Lam, Colin A Semple, Attila Gyenesei, Stefan Mundlos, Uwe Radelof, Hans Lehrach, Paolo Sarmientos, Alexandre Reymond, Duncan R Davidson, Pascal Dollé, Stylianos E Antonarakis, Marie-Laure Yaspo, Salvador Martinez, Richard A Baldock, Gregor Eichele, Andrea Ballabio A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol.: 2011, 9(1);e1000582 PMID:21267068 | PLoS Biol. | Eurexpress transcriptome atlas
  2. Yoshiaki V Nishimura, Tomoyasu Shinoda, Yutaka Inaguma, Hidenori Ito, Koh-Ichi Nagata Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development. Med Mol Morphol: 2012, 45(1);1-6 PMID:22431177
  3. Katsuyoshi Takaoka, Hiroshi Hamada Cell fate decisions and axis determination in the early mouse embryo. Development: 2012, 139(1);3-14 PMID:22147950
  4. William C Skarnes, Barry Rosen, Anthony P West, Manousos Koutsourakis, Wendy Bushell, Vivek Iyer, Alejandro O Mujica, Mark Thomas, Jennifer Harrow, Tony Cox, David Jackson, Jessica Severin, Patrick Biggs, Jun Fu, Michael Nefedov, Pieter J de Jong, A Francis Stewart, Allan Bradley A conditional knockout resource for the genome-wide study of mouse gene function. Nature: 2011, 474(7351);337-42 PMID:21677750
  5. Francisco J Pérez-Cano, Àngels Franch, Cristina Castellote, Margarida Castell The suckling rat as a model for immunonutrition studies in early life. Clin. Dev. Immunol.: 2012, 2012();537310 PMID:22899949 | PMC3415261 | Clin Dev Immunol.
  6. 6.0 6.1 Pawel Krupinski, Vijay Chickarmane, Carsten Peterson Simulating the mammalian blastocyst--molecular and mechanical interactions pattern the embryo. PLoS Comput. Biol.: 2011, 7(5);e1001128 PMID:21573197 | PMC3088645 | PLoS Comput Biol.
  7. Samantha A Morris, Roy T Y Teo, Huiliang Li, Paul Robson, David M Glover, Magdalena Zernicka-Goetz 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.: 2010, 107(14);6364-9 PMID:20308546 | PMC2852013 | PNAS
  8. 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]
  9. 9.0 9.1 Leila Taher, Nicole M Collette, Deepa Murugesh, Evan Maxwell, Ivan Ovcharenko, Gabriela G Loots Global gene expression analysis of murine limb development. PLoS ONE: 2011, 6(12);e28358 PMID:22174793
  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. Melissa H Little, Jane Brennan, Kylie Georgas, Jamie A Davies, Duncan R Davidson, Richard A Baldock, Annemiek Beverdam, John F Bertram, Blanche Capel, Han Sheng Chiu, Dave Clements, Luise Cullen-McEwen, Jean Fleming, Thierry Gilbert, Doris Herzlinger, Derek Houghton, Matt H Kaufman, Elena Kleymenova, Peter A Koopman, Alfor G Lewis, Andrew P McMahon, Cathy L Mendelsohn, Eleanor K Mitchell, Bree A Rumballe, Derina E Sweeney, M Todd Valerius, Gen Yamada, Yiya Yang, Jing Yu A high-resolution anatomical ontology of the developing murine genitourinary tract. Gene Expr. Patterns: 2007, 7(6);680-99 PMID:17452023 | PMC2117077
  14. Yutaka Maeda, Vrushank Davé, Jeffrey A Whitsett Transcriptional control of lung morphogenesis. Physiol. Rev.: 2007, 87(1);219-44 PMID:17237346
  15. Mathias V Schmidt, M Schmidt, L Enthoven, M van der Mark, S Levine, E R de Kloet, M S Oitzl The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int. J. Dev. Neurosci.: 2003, 21(3);125-32 PMID:12711350
  16. J A Beck, S Lloyd, M Hafezparast, M Lennon-Pierce, J T Eppig, M F Festing, E M Fisher Genealogies of mouse inbred strains. Nat. Genet.: 2000, 24(1);23-5 PMID:10615122

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.

Mouse Embryology

  • The e-Mouse Atlas Project EMAP

Mouse Gene Expression

Mouse Genome

Mouse Jackson Laboratory

Mouse Diseases

Mouse Transgenics

Mouse Transgenic Facilities

Mouse Urogenital

Mouse Unsorted Links



Animal Development: Axolotl | Bat | Cat | Chicken | Cow | Dog | Dolphin | Echidna | Fly | Frog | Grasshopper | Guinea Pig | Hamster | Kangaroo | Koala | Lizard | Medaka | Mouse | Pig | Platypus | Rabbit | Rat | Sea Squirt | Sea Urchin | Sheep | Worm | Zebrafish | Life Cycles | Development Timetable | K12
Historic Animals: 1897 Pig | 1900 Chicken | 1901 Lungfish | 1904 Sand Lizard | 1905 Rabbit | 19066 Deer | 1907 Tarsiers | 1908 Human | 1909 Northern Lapwing | 1909 South American and African Lungfish | 1910 Salamander | Embryology History | Historic Disclaimer

Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols


Cite this page: Hill, M.A. (2014) Embryology Mouse Development. Retrieved April 16, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Mouse_Development

What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
Personal tools
Namespaces

Variants
Actions
Navigation
Medicine
Science
Movies-Audio
Human Embryo
Systems
Abnormal
Animals
Explore
Shortcuts
Toolbox