Hoxa5: A Key Player in Development and Disease.
Hoxa5: A Key Player in Development and Disease.
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DOI：
10.3390/jdb4020013
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发表时间：
2016-03-25
影响因子：
2.7
通讯作者：
Landry-Truchon K
中科院分区：
文献类型：
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作者：
Jeannotte L;Gotti F;Landry-Truchon K
Hox基因在发育层次中占据关键位置，它编码转录因子。Hox基因在指定胚胎轴沿着的区域特征和调节形态发生方面至关重要。在小鼠中，Hox基因的靶向突变会导致骨骼转化和器官缺陷，从而损害生存能力。在这里，我们目前的知识Hoxa 5基因，一个范例的功能和Hox基因的调控。对Hoxa 5 −/−小鼠的表型调查揭示了其在骨骼区域特化和器官发生中的关键作用。大多数Hoxa 5 −/−小鼠在出生时死于呼吸窘迫，这是由于气管和肺形态发育异常以及膈肌神经支配受损。表型的严重性确定了Hoxa 5在肺器官发生中相对于其他Hox基因起主要作用。Hoxa 5还控制消化道形态发生、甲状腺和乳腺发育以及卵巢稳态。据报道，在癌症中Hoxa 5表达失调，表明Hoxa 5参与肿瘤易感性和进展。动态Hoxa 5表达谱受到多个顺式作用序列和反式作用调节因子的转录控制。它还受到表观遗传机制的调节，涉及染色质修饰和microRNA。最后，来源于可变剪接和远端启动子的lncRNA包含Hoxa 5基因座。
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.