HOXA5 plays tissue-specific roles in the developing respiratory system
HOXA5 plays tissue-specific roles in the developing respiratory system
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DOI：
10.1242/dev.152686
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发表时间：
2017-10-01
期刊：
影响因子：
4.6
通讯作者：
Jeannotte, Lucie
中科院分区：
文献类型：
--
作者：
Landry-Truchon, Kim;Houde, Nicolas;Jeannotte, Lucie
Hoxa5对多种器官和组织的发育至关重要。在呼吸系统中，Hoxa5功能的丧失会导致新生儿因呼吸窘迫而死亡。HOXA 5蛋白在呼吸道间充质和中枢神经系统膈运动神经元中的表达使我们使用条件性基因靶向方法来解决这些Hoxa 5表达结构域的个体贡献。Hoxa5在肺上皮中不起细胞自主作用，这与该细胞层中缺乏H0XA 5表达一致。相反，间充质中Hoxa5的消融干扰了气管发育、肺上皮细胞分化和肺生长。此外，运动神经元中Hoxa5的缺失导致异常的膈肌神经支配和肌肉组织以及肺发育不全。它还再现了在无效突变体中观察到的新生儿致死率，表明有缺陷的隔膜是出生时存活率受损的主要原因。因此，Hoxa5具有组织特异性功能，差异有助于呼吸道的形态发生。
Hoxa5 is essential for development of several organs and tissues. In the respiratory system, loss of Hoxa5 function causes neonatal death due to respiratory distress. Expression of HOXA5 protein in mesenchyme of the respiratory tract and in phrenic motor neurons of the central nervous system led us to address the individual contribution of these Hoxa5 expression domains using a conditional gene targeting approach. Hoxa5 does not play a cell-autonomous role in lung epithelium, consistent with lack of HOXA5 expression in this cell layer. In contrast, ablation of Hoxa5 in mesenchyme perturbed trachea development, lung epithelial cell differentiation and lung growth. Further, deletion of Hoxa5 in motor neurons resulted in abnormal diaphragm innervation and musculature, and lung hypoplasia. It also reproduced the neonatal lethality observed in null mutants, indicating that the defective diaphragm is the main cause of impaired survival at birth. Thus, Hoxa5 possesses tissue-specific functions that differentially contribute to the morphogenesis of the respiratory tract.