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Hoxa5: A Key Player in Development and Disease

A critical position in the developmental hierarchy is occupied by the Hox genes, which encode transcription factors. Hox genes are crucial in specifying regional identity along the embryonic axes and in regulating morphogenesis. In mouse, targeted mutations of Hox genes cause skeletal transformation...

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Autores principales: Jeannotte, Lucie, Gotti, Florian, Landry-Truchon, Kim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831783/
https://www.ncbi.nlm.nih.gov/pubmed/29615582
http://dx.doi.org/10.3390/jdb4020013
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author Jeannotte, Lucie
Gotti, Florian
Landry-Truchon, Kim
author_facet Jeannotte, Lucie
Gotti, Florian
Landry-Truchon, Kim
author_sort Jeannotte, Lucie
collection PubMed
description A critical position in the developmental hierarchy is occupied by the Hox genes, which encode transcription factors. Hox genes are crucial in specifying regional identity along the embryonic axes and in regulating morphogenesis. In mouse, targeted mutations of Hox genes cause skeletal transformations and organ defects that can impair viability. Here, we present the current knowledge about the Hoxa5 gene, a paradigm for the function and the regulation of Hox genes. The phenotypic survey of Hoxa5(−/−) mice has unveiled its critical role in the regional specification of the skeleton and in organogenesis. Most Hoxa5(−/−) mice die at birth from respiratory distress due to tracheal and lung dysmorphogenesis and impaired diaphragm innervation. The severity of the phenotype establishes that Hoxa5 plays a predominant role in lung organogenesis versus other Hox genes. Hoxa5 also governs digestive tract morphogenesis, thyroid and mammary glands development, and ovary homeostasis. Deregulated Hoxa5 expression is reported in cancers, indicating Hoxa5 involvement in tumor predisposition and progression. The dynamic Hoxa5 expression profile is under the transcriptional control of multiple cis-acting sequences and trans-acting regulators. It is also modulated by epigenetic mechanisms, implicating chromatin modifications and microRNAs. Finally, lncRNAs originating from alternative splicing and distal promoters encompass the Hoxa5 locus.
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spelling pubmed-58317832018-03-30 Hoxa5: A Key Player in Development and Disease Jeannotte, Lucie Gotti, Florian Landry-Truchon, Kim J Dev Biol Review A critical position in the developmental hierarchy is occupied by the Hox genes, which encode transcription factors. Hox genes are crucial in specifying regional identity along the embryonic axes and in regulating morphogenesis. In mouse, targeted mutations of Hox genes cause skeletal transformations and organ defects that can impair viability. Here, we present the current knowledge about the Hoxa5 gene, a paradigm for the function and the regulation of Hox genes. The phenotypic survey of Hoxa5(−/−) mice has unveiled its critical role in the regional specification of the skeleton and in organogenesis. Most Hoxa5(−/−) mice die at birth from respiratory distress due to tracheal and lung dysmorphogenesis and impaired diaphragm innervation. The severity of the phenotype establishes that Hoxa5 plays a predominant role in lung organogenesis versus other Hox genes. Hoxa5 also governs digestive tract morphogenesis, thyroid and mammary glands development, and ovary homeostasis. Deregulated Hoxa5 expression is reported in cancers, indicating Hoxa5 involvement in tumor predisposition and progression. The dynamic Hoxa5 expression profile is under the transcriptional control of multiple cis-acting sequences and trans-acting regulators. It is also modulated by epigenetic mechanisms, implicating chromatin modifications and microRNAs. Finally, lncRNAs originating from alternative splicing and distal promoters encompass the Hoxa5 locus. MDPI 2016-03-25 /pmc/articles/PMC5831783/ /pubmed/29615582 http://dx.doi.org/10.3390/jdb4020013 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Jeannotte, Lucie
Gotti, Florian
Landry-Truchon, Kim
Hoxa5: A Key Player in Development and Disease
title Hoxa5: A Key Player in Development and Disease
title_full Hoxa5: A Key Player in Development and Disease
title_fullStr Hoxa5: A Key Player in Development and Disease
title_full_unstemmed Hoxa5: A Key Player in Development and Disease
title_short Hoxa5: A Key Player in Development and Disease
title_sort hoxa5: a key player in development and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831783/
https://www.ncbi.nlm.nih.gov/pubmed/29615582
http://dx.doi.org/10.3390/jdb4020013
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