The Dlx5 homeobox gene is essential for vestibular morphogenesis in the mouse embryo through a BMP4-mediated pathway
The Dlx5 homeobox gene is essential for vestibular morphogenesis in the mouse embryo through a BMP4-mediated pathway
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DOI：
10.1006/dbio.2002.0713
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发表时间：
2002-08-01
影响因子：
2.7
通讯作者：
Levi, G
中科院分区：
文献类型：
--
作者：
Merlo, GR;Palerai, L;Levi, G
在小鼠胚胎中，D1 x5在耳基板和囊泡中表达，随后在内耳的半规管中表达。在D1 x5/LacZ等位基因缺失的纯合子小鼠中，观察到前庭区严重的畸形，其特征在于半规管的缺失和内淋巴管的缩短。在耳蜗中观察到轻微缺陷，尽管D1 x5在该区域中不表达。嵴形成严重受损，然而，感觉上皮细胞，识别钙视网膜蛋白免疫染色，存在于D1 x5（-/-）小鼠的前庭上皮。椭圆囊和球囊的斑点存在，但细胞稀疏且错位。半规管的异常形态发生伴随着增殖和凋亡细胞分布的改变。在D1 x5（-/-）胚胎中，Nkx5.1（Hmx 3），Pax 2和Lfng的表达没有变化，而骨形态发生蛋白-4（Bmp 4）的表达急剧减少。值得注意的是，BMP 4已被证明在鸡胚的前庭形态发生中起重要作用。我们认为半规管和前庭内耳的发育需要几个同源异型盒基因的独立控制，这些基因似乎通过严格调节BPM 4表达和细胞分化、增殖和凋亡的区域组织来发挥其功能。(C)2002 Elsevier Science（美国）。
In the mouse embryo, D1x5 is expressed in the otic placode and vesicle, and later in the semicircular canals of the inner ear. In mice homozygous for a null D1x5/LacZ allele, a severe dysmorphogenesis of the vestibular region is observed, characterized by the absence of semicircular canals and the shortening of the endolymphatic duct. Minor defects are observed in the cochlea, although D1x5 is not expressed in this region. Cristae formation is severely impaired; however, sensory epithelial cells, recognized by calretinin immunostaining, are present in the vestibular epithelium of D1x5(-/-) mice. The maculae of utricle and saccule are present but cells appear sparse and misplaced. The abnormal morphogenesis of the semicircular canals is accompanied by an altered distribution of proliferating and apoptotic cells. In the D1x5(-/-) embryos, no changes in expression of Nkx5.1(Hmx3), Pax2, and Lfng have been seen, while expression of bone morphogenetic protein-4 (Bmp4) was drastically reduced. Notably, BMP4 has been shown to play a fundamental role in vestibular morphogenesis of the chick embryo. We propose that development of the semicircular canals and the vestibular inner ear requires the independent control of several homeobox genes, which appear to exert their function via tight regulation of BPM4 expression and the regional organization of cell differentiation, proliferation, and apoptosis. (C) 2002 Elsevier Science (USA).