Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783303198572806144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5831783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT jeannottelucie hoxa5akeyplayerindevelopmentanddisease AT gottiflorian hoxa5akeyplayerindevelopmentanddisease AT landrytruchonkim hoxa5akeyplayerindevelopmentanddisease |