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
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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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