Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development
Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development
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DOI：
10.1002/dvdy.20821
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发表时间：
2006-07-01
影响因子：
2.5
通讯作者：
Jiang, Rulang
中科院分区：
文献类型：
--
作者：
Casey, Liam M.;Lan, Yu;Jiang, Rulang
在哺乳动物的腭裂发生过程中，腭架最初从发育中的舌侧成对的上颌突的内侧垂直生长，然后在舌头上方升高并相互融合，形成完整的次级腭部。在人类和其他哺乳动物中已经有过病理性的腭舌融合的报道，但在正常的上颌发育过程中防止这种异常粘连的分子和细胞机制尚不清楚。我们之前曾报道，Jag2基因缺陷的小鼠患有与腭舌融合相关的腭裂，Jag2基因编码Notch家族受体的细胞表面配体。在这份报告中，我们发现Jag2在整个口腔上皮细胞中都有表达，并且在口腔上皮细胞分化过程中是Notch1激活所必需的。我们发现，在腭部发育过程中，Notch1通常在口腔周皮细胞中高度激活，这些细胞覆盖着发育中的舌头和下颌和上颌突的外侧口腔表面。在Jag2突变体中，口腔周皮Notch1的激活在腭部发育过程中显著减弱。进一步的分子和超微结构分析表明，Jag2突变体的口腔上皮组织和周皮分化受到破坏。此外，在重组外植体培养中，我们发现Jag2突变的舌头融合到了野生型的腭架上。这些数据表明，Jag2-Notch1信号在腭部发育过程中在口腔上皮细胞中受到时空调控，以防止早熟的腭架与其他口腔组织的粘连，并促进升高的腭架之间的正常粘连。
During mammalian palatogenesis, palatal shelves initially grow vertically from the medial sides of the paired maxillary processes flanking the developing tongue and subsequently elevate and fuse with each other above the tongue to form the intact secondary palate. Pathological palate-mandible or palate-tongue fusions have been reported in humans and other mammals, but the molecular and cellular mechanisms that prevent such aberrant adhesions during normal palate development are unknown. We previously reported that mice deficient in Jag2, which encodes a cell surface ligand for the Notch family receptors, have cleft palate associated with palate-tongue fusions. In this report, we show that Jag2 is expressed throughout the oral epithelium and is required for Notch1 activation during oral epithelial differentiation. We show that Notch1 is normally highly activated in the differentiating oral periderm cells covering the developing tongue and the lateral oral surfaces of the mandibular and maxillary processes during palate development. Oral periderm activation of Notch1 is significantly attenuated during palate development in the Jag2 mutants. Further molecular and ultrastructural analyses indicate that oral epithelial organization and periderm differentiation are disrupted in the Jag2 mutants. Moreover, we show that the Jag2 mutant tongue fused to wild-type palatal shelves in recombinant explant cultures. These data indicate that Jag2-Notch1 signaling is spatiotemporally regulated in the oral epithelia during palate development to prevent premature palatal shelf adhesion to other oral tissues and to facilitate normal adhesion between the elevated palatal shelves.