Cargando…
Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation
Although several syndromes include abnormalities of both the ventral body wall and external genitalia, the developmental bases of this correlation are largely unknown. Naturally occurring mutations in Aristaless-like 4 (Alx4, Strong's luxoid: Alx4(Lst)) have ventral body wall and pelvic girdle...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925283/ https://www.ncbi.nlm.nih.gov/pubmed/23942202 http://dx.doi.org/10.1038/ejhg.2013.160 |
_version_ | 1782303840096223232 |
---|---|
author | Matsumaru, Daisuke Haraguchi, Ryuma Moon, Anne M Satoh, Yoshihiko Nakagata, Naomi Yamamura, Ken-ichi Takahashi, Naoki Kitazawa, Sohei Yamada, Gen |
author_facet | Matsumaru, Daisuke Haraguchi, Ryuma Moon, Anne M Satoh, Yoshihiko Nakagata, Naomi Yamamura, Ken-ichi Takahashi, Naoki Kitazawa, Sohei Yamada, Gen |
author_sort | Matsumaru, Daisuke |
collection | PubMed |
description | Although several syndromes include abnormalities of both the ventral body wall and external genitalia, the developmental bases of this correlation are largely unknown. Naturally occurring mutations in Aristaless-like 4 (Alx4, Strong's luxoid: Alx4(Lst)) have ventral body wall and pelvic girdle abnormalities. We sought to determine whether the development of the genital tubercle (GT) and its derivatives, the external genitalia, is affected by this mutation. We thus performed genetic and tissue labeling analyses in mutant mice. Alx4(Lst/Lst) mutants displayed hypoplasia of the dorsal GT and reduced expression of Fibronectin. We analyzed cell migration during GT formation by tissue labeling experiments and discovered that the cells located in the proximal segment of the umbilical cord (infra-umbilical mesenchyme) migrate toward the dorsal part of the GT. The Alx4(Lst/Lst) mutants also displayed augmented expression of Hh signal-related genes. Hence, we analyzed a series of combinatorial mutants for Alx4, Sonic hedgehog (Shh) and GLI-Kruppel family member 3 (Gli3). These phenotype–genotype analyses suggested a genetic interaction between Alx4 and Hh signaling during GT formation. Moreover, Hh gain-of-function mutants phenocopied some of these phenotypes. These observations reveal novel information regarding the pathogenic mechanisms of syndromic lower ventral body malformations, which are largely unknown. |
format | Online Article Text |
id | pubmed-3925283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39252832014-03-01 Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation Matsumaru, Daisuke Haraguchi, Ryuma Moon, Anne M Satoh, Yoshihiko Nakagata, Naomi Yamamura, Ken-ichi Takahashi, Naoki Kitazawa, Sohei Yamada, Gen Eur J Hum Genet Article Although several syndromes include abnormalities of both the ventral body wall and external genitalia, the developmental bases of this correlation are largely unknown. Naturally occurring mutations in Aristaless-like 4 (Alx4, Strong's luxoid: Alx4(Lst)) have ventral body wall and pelvic girdle abnormalities. We sought to determine whether the development of the genital tubercle (GT) and its derivatives, the external genitalia, is affected by this mutation. We thus performed genetic and tissue labeling analyses in mutant mice. Alx4(Lst/Lst) mutants displayed hypoplasia of the dorsal GT and reduced expression of Fibronectin. We analyzed cell migration during GT formation by tissue labeling experiments and discovered that the cells located in the proximal segment of the umbilical cord (infra-umbilical mesenchyme) migrate toward the dorsal part of the GT. The Alx4(Lst/Lst) mutants also displayed augmented expression of Hh signal-related genes. Hence, we analyzed a series of combinatorial mutants for Alx4, Sonic hedgehog (Shh) and GLI-Kruppel family member 3 (Gli3). These phenotype–genotype analyses suggested a genetic interaction between Alx4 and Hh signaling during GT formation. Moreover, Hh gain-of-function mutants phenocopied some of these phenotypes. These observations reveal novel information regarding the pathogenic mechanisms of syndromic lower ventral body malformations, which are largely unknown. Nature Publishing Group 2014-03 2013-08-14 /pmc/articles/PMC3925283/ /pubmed/23942202 http://dx.doi.org/10.1038/ejhg.2013.160 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Matsumaru, Daisuke Haraguchi, Ryuma Moon, Anne M Satoh, Yoshihiko Nakagata, Naomi Yamamura, Ken-ichi Takahashi, Naoki Kitazawa, Sohei Yamada, Gen Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title | Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title_full | Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title_fullStr | Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title_full_unstemmed | Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title_short | Genetic analysis of the role of Alx4 in the coordination of lower body and external genitalia formation |
title_sort | genetic analysis of the role of alx4 in the coordination of lower body and external genitalia formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925283/ https://www.ncbi.nlm.nih.gov/pubmed/23942202 http://dx.doi.org/10.1038/ejhg.2013.160 |
work_keys_str_mv | AT matsumarudaisuke geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT haraguchiryuma geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT moonannem geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT satohyoshihiko geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT nakagatanaomi geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT yamamurakenichi geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT takahashinaoki geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT kitazawasohei geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation AT yamadagen geneticanalysisoftheroleofalx4inthecoordinationoflowerbodyandexternalgenitaliaformation |