Dorsoventral Patterning of the Mouse Coat by Tbx15

Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (deH), affects dorsoventral skin characteristics, especia...

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Main Authors:	Candille, Sophie I, Raamsdonk, Catherine D. Van, Chen, Changyou, Kuijper, Sanne, Chen-Tsai, Yanru, Russ, Andreas, Meijlink, Frits, Barsh, Gregory S
Format:	Online
Language:	English
Published:	Public Library of Science 2004
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC314463/

id	pubmed-314463
recordtype	oai_dc
spelling	pubmed-3144632004-01-20 Dorsoventral Patterning of the Mouse Coat by Tbx15 Candille, Sophie I Raamsdonk, Catherine D. Van Chen, Changyou Kuijper, Sanne Chen-Tsai, Yanru Russ, Andreas Meijlink, Frits Barsh, Gregory S Research Article Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (deH), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (at) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the deH mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in deH that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in deH/deH animals. Construction of a targeted allele of Tbx15 confirmed that the deH phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie region-specific differences in body morphology. Public Library of Science 2004-01 2004-01-20 /pmc/articles/PMC314463/ /pubmed/14737183 http://dx.doi.org/10.1371/journal.pbio.0020003 Text en Copyright: © 2004 Candille et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Candille, Sophie I Raamsdonk, Catherine D. Van Chen, Changyou Kuijper, Sanne Chen-Tsai, Yanru Russ, Andreas Meijlink, Frits Barsh, Gregory S
spellingShingle	Candille, Sophie I Raamsdonk, Catherine D. Van Chen, Changyou Kuijper, Sanne Chen-Tsai, Yanru Russ, Andreas Meijlink, Frits Barsh, Gregory S Dorsoventral Patterning of the Mouse Coat by Tbx15
author_facet	Candille, Sophie I Raamsdonk, Catherine D. Van Chen, Changyou Kuijper, Sanne Chen-Tsai, Yanru Russ, Andreas Meijlink, Frits Barsh, Gregory S
author_sort	Candille, Sophie I
title	Dorsoventral Patterning of the Mouse Coat by Tbx15
title_short	Dorsoventral Patterning of the Mouse Coat by Tbx15
title_full	Dorsoventral Patterning of the Mouse Coat by Tbx15
title_fullStr	Dorsoventral Patterning of the Mouse Coat by Tbx15
title_full_unstemmed	Dorsoventral Patterning of the Mouse Coat by Tbx15
title_sort	dorsoventral patterning of the mouse coat by tbx15
description	Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (deH), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (at) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the deH mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in deH that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in deH/deH animals. Construction of a targeted allele of Tbx15 confirmed that the deH phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie region-specific differences in body morphology.
publisher	Public Library of Science
publishDate	2004
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC314463/
_version_	1611367819181555712

Dorsoventral Patterning of the Mouse Coat by Tbx15

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