Hand2 is required in the epithelium for palatogenesis in mice.
Hand2 is required in the epithelium for palatogenesis in mice.
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DOI：
10.1016/j.ydbio.2009.03.021
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发表时间：
2009-06-01
影响因子：
2.7
通讯作者：
Chen, YiPing
中科院分区：
文献类型：
--
作者：
Xiong, Wei;He, Fenglei;Morikawa, Yuka;Yu, Xueyan;Zhang, Zunyi;Lan, Yu;Jiang, Rulang;Cserjesi, Peter;Chen, YiPing
碱性螺旋-环-螺旋（bHLH）转录因子Hand2参与了包括颅面器官在内的多个器官的发育。携带Hand2亚型等位基因（Hand2LoxP/−）的小鼠表现为腭裂表型。Hand2鳃弓特异性增强子的特异性缺失也会导致小鼠下颌骨发育不全和腭裂的形成。然而，Hand2调控腭发育的潜在机制尚不清楚。我们发现Hand2在发育中的上颚上皮和间质中均有表达。虽然间充质特异性的Hand2失活对腭裂发育没有影响，但上皮特异性的Hand2缺失会产生腭裂表型。Hand2似乎在前腭和后腭中发挥着不同的作用。在Hand2LoxP/−小鼠的前腭，观察到外周细胞的过早死亡和内侧边缘上皮（MEE） Shh的下调，并伴有腭间质细胞增殖水平的降低。在后腭，低剂量的Hand2可导致上皮表面的外周细胞异常死亡，引发腭架与下颌骨之间的异常融合，阻止腭架升高。我们进一步证明BMP的活性对Hand2在上颚的表达至关重要。我们得出结论，Hand2是上皮的内在调节因子，是腭发育所必需的。
The basic helix-loop-helix (bHLH) transcription factor Hand2 has been implicated in the development of multiple organs, including craniofacial organs. Mice carrying Hand2 hypomorphic alleles (Hand2LoxP/−) display a cleft palate phenotype. A specific deletion of the Hand2 branchial arch-specific enhancer also leads to a hypoplastic mandible and cleft palate formation in mice. However, the underlying mechanism of Hand2 regulation of palate development remains unknown. Here we show that Hand2 is expressed in both the epithelium and mesenchyme of the developing palate. While mesenchymal specific inactivation of Hand2 has no impact on palate development, epithelial specific deletion of Hand2 creates a cleft palate phenotype. Hand2 appears to exert distinct roles in the anterior and posterior palate. In the anterior palate of Hand2LoxP/− mice, premature death of periderm cells and a down-regulation of Shh are observed in the medial edge epithelium (MEE), accompanied by a decreased level of cell proliferation in the palatal mesenchyme. In the posterior palate, a lower dose of Hand2 causes aberrant periderm cell death on the surface of the epithelium, triggering abnormal fusion between the palatal shelf and mandible and preventing palatal shelf elevation. We further demonstrate that BMP activities are essential for the expression of Hand2 in the palate. We conclude that Hand2 is an intrinsic regulator in the epithelium and is required for palate development.
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