|Embryology - 18 Feb 2019 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Movies
- 4 Animal Model Comparison
- 5 Oocyte Development
- 6 Early Mouse Development
- 7 Later Mouse Development
- 8 Mouse Limb
- 9 Carnegie Stages Comparison
- 10 Placenta Development
- 11 Spermatozoa Development
- 12 Limb Development
- 13 Neural Development
- 14 Urogenital Development
- 15 Lung Development
- 16 Endocrine Development
- 17 Mouse Knockouts
- 18 The Genealogy Chart of Inbred Strains
- 19 Mouse Genome
- 20 Animal Model Differences
- 21 References
- 22 Additional Images
- 23 External Links
- 24 Glossary Links
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.
|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 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
|Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison|
|Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | Medaka | Category:Timeline|
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
<pubmed limit=5>Mouse Development</pubmed>
|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.
The collapsible tables below contain a number of movies showing aspects of mouse development.
- Links: Movies
Animal Model Comparison
|Postnatal Animal Models||mouse||rat||pig|
|Pregnancy period (days)||18 – 21||21 – 23||110 – 118|
|Placenta type||Discoidal, decidual
|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) Links: timeline|
Mouse oogenesis 
Early Mouse Development
|zygote||blastomeres||morula||early blastocyst||hatched blastocyst|
Early mouse development model
|Live cell imaging and tracking
||Simulation of Zygote to Blastocyst
- Links: Mouse Stages
Later Mouse Development
- Links: Limb Development
Carnegie Stages Comparison
The table below gives an approximate comparison of human, mouse and rat embryos based upon Carnegie staging.
|Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison|
- Uterine radial artery branches into 5-10 dilated spiral arteries.
- Spiral arteries then converge at the trophoblast giant cell layer and empty into straight trophoblast-lined "canals".
- 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.
- Labyrinth - (equivalent to human villi) a selective barrier on the fetal side, is an array of fetal and maternal vessels.
- 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.
- Giant cells - next to the uterine cells form the outermost fetal cell layer until (E 12).
|Mouse Placenta Vasculature (E16.5)|
|superior view (maternal side)||lateral view (maternal side at bottom)|
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.
Mouse limb skeleton cartoon
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.
Change in cell types and tissue formation as a function of mouse developmental stage.
- Links: Limb Development
The data below is summarised from a study of early neural development in the mouse.
- 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
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.
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.
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
Vertebrate lung development is generally divided into 5 stages, based upon growth and histological appearance. Mouse age data
|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
|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|
Note that while human third trimester fetus has regular respiratory breathing movements, the common mouse model (C57BL/6J} completely lacks these movements.
Respiratory Species Comparison
|Respiratory Stages - Species Comparison - Stages Gestational age (days)|
|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|
|Data modified from|
The following images are from a recent study of the development of bronchial branching in he mouse between E10 to E14.
Mesenchyme (red) and epithelium (blue) the study used knockout mice to show the role of Wnt signalling in branching morphogenesis.
Two postnatal phases identified:
- 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.
- 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.
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
The Genealogy Chart of Inbred Strains
This Nature paper 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 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
Animal Model Differences
pancreas - "In contrast to the published data from mouse embryos, during human pancreas development, we detected only a single-phase of Neurogenin 3 (NEUROG3) expression and endocrine differentiation from approximately 8 weeks, before which Nirenberg and Kim homeobox 2.2 (NKX2.2) was not observed in the pancreatic progenitor cell population. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue."
White pulp - Human white pulp has three stromal cell types of different phenotype and location.
Red pulp - mouse and human red pulp sinusoid circulation differs.
- mouse - circulation is closed, afferent arterial blood to the red pulp sinusoids, and to the marginal zone sinus.
- humans - circulation is open, no connection from capillaries to sinuses in the red pulp.
Contrasting mechanisms of penile urethral formation in mouse and human "This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed."
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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.
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- The e-Mouse Atlas Project EMAP
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 Imaging Centre
- Gude, W. D. (2012). Histological atlas of the laboratory mouse. Retrieved from https://ebookcentral.proquest.com
- NCBI- Mouse Genome Sequencing
- Mouse Genome Informatics
- EBI- Mouse Genome Sequencing
- ANEX Rat and Mouse Database - (University of Tokushima)
- Genetic and Physical Maps of the Mouse Genome (Whitehead Institute/MIT)
- Genetic Location Database (University of Southampton)
- Koop Human and Mouse Genome Project Research (University of Victoria)
- Genome Systems, Inc.
Mouse Jackson Laboratory
- Jackson Laboratory
- Jackson Laboratory Induced Mutant Resource
- Jackson Laboratory BioInformatics Electronic Bulletin Board System
- Mouse Inbred Strains (Jackson Labs)
- Mouse Linkage Map
- Mouse Nomenclature Rules and Guidelines (Jackson Labs)
- Helicobacter hepaticus, a Recently Recognized Bacterial Pathogen, Associated with Chronic Hepatitis and Hepatocellular Neoplasia in Laboratory Mice (CDC)
- Helicobacter Infection in Laboratory Mice: History, Significance, Detection and Management (Charles River)
- Infectious Diseases of Mice and Rats (NAS-ILAR)
- Infectious Diseases of Mice and Rats Companion Guide (NAS-ILAR)
- Infectious Diseases of Mice and Rats (AFIP-POLA)
- Murine Helicobacters (NCI)
- NIH List of Available Knockout Mice | Factsheet
- International Knockout Mouse Consortium IKMC | Research using IKMC products
- NC3Rs Mouse databases
- Mammary Transgene Database (Baylor College of Medicine)
- TBASE - Transgenic/Targeted Mutation Database
- B Universal Ltd.
- BIG BLUE (Big Blue Transgenic Mouse Mailing List Archives)
- Big Blue lacI Transgenic Mouse Page
- Charles River Laboratories, Inc.
- Chrysalis DNX Transgenic Services
Mouse Transgenic Facilities
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- GenitoUrinary Development Molecular Anatomy Project (GUDMAP) Renal Development Tutorial | Genital Development Tutorial
Mouse Unsorted Links
- Covance Research Products
- Edison Biotechnology Institute (Ohio University)
- Encyclopedia of the Mouse Genome (Jackson Laboratory)
- EUCIB Mouse Backcross Database (MBx)
- Harlan Sprague Dawley, Inc.
- It's a Knockout
- Jackson Laboratory Gopher Server
- Lane List of Named Mutations and Polymorphic Loci
- Lexicon Genetics, Inc.
- Lymphocytic Choriomeningitis Virus: An Unrecognized Teratogenic Pathogen (CDC)
- M & B Breeding and Research Centre Ltd.
- Map Manager Software
- Mice and Men: Making the Most of Our Similarities (ORNL)
- Microinjection Workshop
- Mouse Atlas and Gene Expression Database Project
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- MRC Mouse Genome Centre
- National Institute of Genetics Mouse Genetic Resources (Japan)
- NIH Animal Genetic Resource
- NIH Directory of Transgenic Mice
- NIH Mouse Club
- Of Mice and Men (HHMI's Blazing a Genetic Trail)
- Online Mendelian Inheritance in Animals (University of Sydney)
- Pathology of Genetically-altered Mice
- Portable Dictionary of the Mouse Genome
- Review of Pasteurella pneumotropica (Charles River)
- The Mouse in Science: Cancer Research
- The Mouse in Science: Monoclonal Antibodies
- The Mouse in Science: Vaccines
- The Mouse in Science: Why Mice?