Mouse Development - Revision history

Z8600021 at 22:58, 1 December 2021

2021-12-01T22:58:48Z

← Older revision		Revision as of 08:58, 2 December 2021
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			* '''Ex Utero Culture of Mouse Embryos from Pregastrulation to Advanced Organogenesis''' {{#pmid:34747408\|PMID34747408}} "Postimplantation mammalian embryo culture methods have been generally inefficient and limited to brief periods after dissection out of the uterus. Platforms have been recently developed for highly robust and prolonged ex utero culture of mouse embryos from egg-cylinder stages until advanced organogenesis. These platforms enable appropriate and faithful development of pregastrulating embryos (E5.5) until the hind limb formation stage (E11). Late gastrulating embryos (E7.5) are grown in rotating bottles in these settings, while extended culture from pregastrulation stages (E5.5 or E6.5) requires a combination of static and rotating bottle cultures. In addition, sensitive regulation of O2 and CO2 concentration, gas pressure, glucose levels, and the use of a specific ex utero culture medium are critical for proper embryo development. Here, a detailed step-by-step protocol for extended ex utero mouse embryo culture is provided. The ability to grow normal mouse embryos ex utero from gastrulation to organogenesis represents a valuable tool for characterizing the effect of different experimental perturbations during embryonic development."

	* '''Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo''' {{#pmid:31222057\|PMID31222057}} "Our computational analysis focuses on the 32- to 64-cell {{mouse}} embryo transition, Embryonic day (3.25), whose study in literature is concentrated mainly on the search for an early onset of the second cell-fate decision, the specification of the inner cell mass (ICM) to primitive endoderm (PE) and epiblast (EPI). We analysed single-cell (sc) microarray transcriptomics data from E3.25 using Hierarchical Optimal k-Means (HOkM) clustering, and identified two groups of ICM cells: a group of cells from embryos with less than 34 cells (E3.25-LNCs), and another group of cells from embryos with more than 33 cells (E3.25-HNCs), corresponding to two developmental stages. Although we found massive underlying heterogeneity in the ICM cells at E3.25-HNC with over 3,800 genes with transcriptomics bifurcation, many of which are PE and EPI markers, we showed that the E3.25-HNCs are neither PE nor EPI. Importantly, analysing the differently expressed genes between the E3.25-LNCs and E3.25-HNCs, we uncovered a non-autonomous mechanism, based on a minimal number of four inner-cell contacts in the ICM, which activates Oct4 in the preimplantation embryo. Oct4 is highly expressed but unstable at E3.25-LNC, and stabilizes at high level at E3.25-HNC, with Bsg highly expressed, and the chromatin remodelling program initialised to establish an early naïve pluripotent state. Our results indicate that the pluripotent state we found to exist in the ICM at E3.25-HNC is the in vivo counterpart of a new, very early pluripotent state. We compared the transcriptomics profile of this in vivo E3.25-HNC pluripotent state, together with the profiles of E3.25-LNC, E3.5 EPI and E4.5 EPI cells, with the profiles of all embryonic stem cells (ESCs) available in the GEO database from the same platform (over 600 microarrays)."		* '''Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo''' {{#pmid:31222057\|PMID31222057}} "Our computational analysis focuses on the 32- to 64-cell {{mouse}} embryo transition, Embryonic day (3.25), whose study in literature is concentrated mainly on the search for an early onset of the second cell-fate decision, the specification of the inner cell mass (ICM) to primitive endoderm (PE) and epiblast (EPI). We analysed single-cell (sc) microarray transcriptomics data from E3.25 using Hierarchical Optimal k-Means (HOkM) clustering, and identified two groups of ICM cells: a group of cells from embryos with less than 34 cells (E3.25-LNCs), and another group of cells from embryos with more than 33 cells (E3.25-HNCs), corresponding to two developmental stages. Although we found massive underlying heterogeneity in the ICM cells at E3.25-HNC with over 3,800 genes with transcriptomics bifurcation, many of which are PE and EPI markers, we showed that the E3.25-HNCs are neither PE nor EPI. Importantly, analysing the differently expressed genes between the E3.25-LNCs and E3.25-HNCs, we uncovered a non-autonomous mechanism, based on a minimal number of four inner-cell contacts in the ICM, which activates Oct4 in the preimplantation embryo. Oct4 is highly expressed but unstable at E3.25-LNC, and stabilizes at high level at E3.25-HNC, with Bsg highly expressed, and the chromatin remodelling program initialised to establish an early naïve pluripotent state. Our results indicate that the pluripotent state we found to exist in the ICM at E3.25-HNC is the in vivo counterpart of a new, very early pluripotent state. We compared the transcriptomics profile of this in vivo E3.25-HNC pluripotent state, together with the profiles of E3.25-LNC, E3.5 EPI and E4.5 EPI cells, with the profiles of all embryonic stem cells (ESCs) available in the GEO database from the same platform (over 600 microarrays)."

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	<html5media width="550" height="360">https://www.youtube.com/embed/P4kP0Eg348I</html5media>		<html5media width="550" height="360">https://www.youtube.com/embed/P4kP0Eg348I</html5media>

	* '''Conserved and Divergent Features of Human and Mouse Kidney Organogenesis'''{{#pmid:29449453\|PMID29449453}} "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 {{ME15.5}} 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 {{ME7.5}} to {{ME18.5}}'''{{#pmid:28891434\|PMID28891434}} "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}}{{#pmid:20805319\|PMID20805319}}{{#pmid:26961180\|PMID26961180}}, {{heart}}{{#pmid:19359541\|PMID19359541}}}		* '''Histology Atlas of the Developing Prenatal and Postnatal Mouse Central Nervous System, with Emphasis on Prenatal Days {{ME7.5}} to {{ME18.5}}'''{{#pmid:28891434\|PMID28891434}}

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	\| {{Older papers}}		\| {{Older papers}}
			* '''Conserved and Divergent Features of Human and Mouse Kidney Organogenesis'''{{#pmid:29449453\|PMID29449453}} "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 {{ME15.5}} 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 {{ME7.5}} to {{ME18.5}}'''{{#pmid:28891434\|PMID28891434}} "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}}{{#pmid:20805319\|PMID20805319}}{{#pmid:26961180\|PMID26961180}}, {{heart}}{{#pmid:19359541\|PMID19359541}}}

	* '''Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development'''{{#pmid:22431177\|PMID22431177}} "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."		* '''Application of in utero electroporation and live imaging in the analyses of neuronal migration during mouse brain development'''{{#pmid:22431177\|PMID22431177}} "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."

Z8600021 at 03:23, 20 Mayıs 2020

2020-05-20T03:23:39Z

← Older revision		Revision as of 13:23, 20 Mayıs 2020
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	==Neural Development==		==Neural Development==
	The ~~data below is summarised from a study~~ of ~~early neural development in the mouse~~.{{#pmid:~~2712345~~\|~~PMID2712345~~}}		The adult mouse brain consist of approximately 70 million neurons.{{#pmid:16880386\|PMID16880386}}

	* 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		===Early Neural Development===

			'''Neural Fold Fusion'''{{#pmid:2712345\|PMID2712345}}
			* first fusion - 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).		* second fusion - at the original rostral end of the neural plate (rostrodorsally).
	* third fusion - in the caudal diencephalon (rostrally and caudally)		* third fusion - in the caudal diencephalon (rostrally and caudally)

Z8600021 at 23:31, 23 December 2019

2019-12-23T23:31:23Z

← Older revision		Revision as of 09:31, 24 December 2019
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	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 over 450 different strains of inbred research mice, and these strains have recently been organized into a chart. The deer mouse (''Peromyscus maniculatus''){{#pmid:26930071\|PMID26930071}} lives in the Americas and is closely related to the white-footed mouse. Those interested in the mouse reproductive cycle should also look at the mouse estrous cycle.

Z8600021 at 03:29, 29 July 2019

2019-07-29T03:29:55Z

← Older revision		Revision as of 13:29, 29 July 2019
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	{{Mouse links}}		{{Mouse links}}

			<br>
	{{Mouse E days}}		{{Mouse E days}}
	== Some Recent Findings ==		== Some Recent Findings ==

Z8600021 at 01:08, 1 July 2019

2019-07-01T01:08:32Z

← Older revision		Revision as of 11:08, 1 July 2019
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	==Oocyte Development==		==Oocyte Development==
			The Mose {{oocyte}} reaches a maximum size of 70 μm in diameter in a follicle 125 μm in diameter, followed by ongoing follicle growth theca interns and antrum development.<ref name=Brambell1928{{Ref-Brambell1928}}</ref>

	Mouse oogenesis {{#pmid:28841213\|PMID28841213}}		Mouse oogenesis {{#pmid:28841213\|PMID28841213}}

Z8600021 at 00:58, 1 July 2019

2019-07-01T00:58:42Z

← Older revision		Revision as of 10:58, 1 July 2019
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	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Mouse+Development''Mouse Development'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Mouse+Development''Mouse Development'']

	~~<pubmed limit=5>Mouse Development</pubmed>~~
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"

Z8600021 at 02:38, 27 Haziran 2019

2019-06-27T02:38:58Z

← Older revision		Revision as of 12:38, 27 Haziran 2019
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			* '''Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo''' {{#pmid:31222057\|PMID31222057}} "Our computational analysis focuses on the 32- to 64-cell {{mouse}} embryo transition, Embryonic day (3.25), whose study in literature is concentrated mainly on the search for an early onset of the second cell-fate decision, the specification of the inner cell mass (ICM) to primitive endoderm (PE) and epiblast (EPI). We analysed single-cell (sc) microarray transcriptomics data from E3.25 using Hierarchical Optimal k-Means (HOkM) clustering, and identified two groups of ICM cells: a group of cells from embryos with less than 34 cells (E3.25-LNCs), and another group of cells from embryos with more than 33 cells (E3.25-HNCs), corresponding to two developmental stages. Although we found massive underlying heterogeneity in the ICM cells at E3.25-HNC with over 3,800 genes with transcriptomics bifurcation, many of which are PE and EPI markers, we showed that the E3.25-HNCs are neither PE nor EPI. Importantly, analysing the differently expressed genes between the E3.25-LNCs and E3.25-HNCs, we uncovered a non-autonomous mechanism, based on a minimal number of four inner-cell contacts in the ICM, which activates Oct4 in the preimplantation embryo. Oct4 is highly expressed but unstable at E3.25-LNC, and stabilizes at high level at E3.25-HNC, with Bsg highly expressed, and the chromatin remodelling program initialised to establish an early naïve pluripotent state. Our results indicate that the pluripotent state we found to exist in the ICM at E3.25-HNC is the in vivo counterpart of a new, very early pluripotent state. We compared the transcriptomics profile of this in vivo E3.25-HNC pluripotent state, together with the profiles of E3.25-LNC, E3.5 EPI and E4.5 EPI cells, with the profiles of all embryonic stem cells (ESCs) available in the GEO database from the same platform (over 600 microarrays)."

	* '''Molecular recording of mammalian embryogenesis'''{{#pmid:31086336\|PMID31086336}} "Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes."		* '''Molecular recording of mammalian embryogenesis'''{{#pmid:31086336\|PMID31086336}} "Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes."

Z8600021 at 00:06, 19 Haziran 2019

2019-06-19T00:06:48Z

← Older revision		Revision as of 10:06, 19 Haziran 2019
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			* '''Molecular recording of mammalian embryogenesis'''{{#pmid:31086336\|PMID31086336}} "Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes."

	* '''In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level'''<ref>McDole K. etal., [https://www.cell.com/cell/fulltext/S0092-8674(18)31243-1 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</ref> "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." [https://www.youtube.com/watch?v=P4kP0Eg348I YouTube]		* '''In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level'''<ref>McDole K. etal., [https://www.cell.com/cell/fulltext/S0092-8674(18)31243-1 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</ref> "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." [https://www.youtube.com/watch?v=P4kP0Eg348I YouTube]

Z8600021 at 03:25, 12 February 2019

2019-02-12T03:25:20Z

← Older revision		Revision as of 13:25, 12 February 2019
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	{{spleen}} - mouse and human red pulp sinusoid circulation differs.{{#pmid:21525186\|PMID21525186}}
	* mouse - circulation is closed, afferent arterial blood to the red pulp sinusoids, and to the marginal zone sinus.		{{spleen}}
	* humans - circulation is open, no connection from capillaries to sinuses in the red pulp.
			White pulp - Human white pulp has three stromal cell types of different phenotype and location.{{#pmid:25827019\|PMID25827019}}

			Marginal zone - only in {{mouse}} and {{rat}} between white and red pulp an additional B-cell compartment.{{#pmid:25827019\|PMID25827019}}

			Red pulp - mouse and human red pulp sinusoid circulation differs.{{#pmid:21525186\|PMID21525186}}
			** 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.

Z8600021 at 01:51, 4 February 2019

2019-02-04T01:51:01Z

← Older revision		Revision as of 11:51, 4 February 2019
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	==Animal Model Differences==		==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."{{#pmid:23630303 \|PMID23630303 }}


			{{spleen}} - mouse and human red pulp sinusoid circulation differs.{{#pmid:21525186\|PMID21525186}}
			* 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.

	{{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."{{#pmid:23630303 \|PMID23630303 }}

			{{urethra}}

	* '''Contrasting mechanisms of penile {{urethra}}l formation in mouse and human'''{{#pmid:29859371\|PMID29859371}} "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."		'''Contrasting mechanisms of penile {{urethra}}l formation in mouse and human'''{{#pmid:29859371\|PMID29859371}} "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."