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Hoxa5: A Key Player in Development and Disease

Centre de recherche sur le cancer de l′Université Laval; CRCHU de Québec, L′Hôtel-Dieu de Québec, QC G1R 3S3, Canada
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, QC G1V 0A6, Canada
Author to whom correspondence should be addressed.
Academic Editor: Vincenzo Zappavigna
J. Dev. Biol. 2016, 4(2), 13;
Received: 15 January 2016 / Revised: 8 March 2016 / Accepted: 16 March 2016 / Published: 25 March 2016
(This article belongs to the Special Issue Hox Genes and Development)
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. View Full-Text
Keywords: Hox genes; organogenesis; tumorigenesis; gene regulation; long non-coding RNA Hox genes; organogenesis; tumorigenesis; gene regulation; long non-coding RNA
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Jeannotte, L.; Gotti, F.; Landry-Truchon, K. Hoxa5: A Key Player in Development and Disease. J. Dev. Biol. 2016, 4, 13.

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