mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes
mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes
复制标题
mab21-l3 调节多纤毛细胞和离子细胞的细胞命运规范
DOI：
10.1038/ncomms7017
复制
发表时间：
2015
影响因子：
16.6
通讯作者：
Koichi Miyatake and Eisuke Nishida
中科院分区：
文献类型：
--
作者：
Chika Takahashi;Morioh Kusakabe;Toshiyasu Suzuki;Koichi Miyatake and Eisuke Nishida
多纤毛细胞（MCC）和离子细胞的细胞命运规格通常在发育中的上皮中被Notch通路抑制，但由不同的主调节器控制，这表明存在将Notch通路与MCC和离子细胞规格连接的共同调节器。在这里，我们表明，mab 21家族基因，mab 21-l3，代表缺失的环节。在异种胚胎表皮中，mab 21 - 13的表达特异性地发现于MCC和离子细胞中，并且通过Notch途径下调。在Xenopus中敲低mab 21 - 13下调MCC特异性和离子细胞特异性主基因，导致MCC和离子细胞的急剧损失。在小鼠气管上皮细胞中，mab 21 - 13的表达也被Notch途径下调，并且是MCC分化所必需的。此外，mab 21 - 13功能的条件性获得挽救了Notch诱导的非洲爪蟾MCC和离子细胞的损失。这些结果表明mab 21 - 13在MCC和离子细胞的细胞命运规范中作用于Notch途径的下游。
Cell fate specifications of multiciliate cells (MCCs) and ionocytes are commonly suppressed by the Notch pathway in developing epithelia, but are governed by different master regulators, suggesting the existence of a common regulator linking the Notch pathway to both MCC and ionocyte specifications. Here we show that a mab21 family gene,mab21-l3, represents the missing link. InXenopusembryonic epidermis,mab21-l3expression is specifically found in MCCs and ionocytes and is downregulated by the Notch pathway. Knockdown ofmab21-l3inXenopusdownregulates both MCC-specific and ionocyte-specific master genes, resulting in drastic loss of MCCs and ionocytes. In mouse tracheal epithelial cells,mab21-l3expression is also downregulated by the Notch pathway and is required for MCC differentiation. Moreover, conditional gain of function ofmab21-l3rescues Notch-induced loss of MCCs and ionocytes inXenopus. These results indicate thatmab21-l3acts downstream of the Notch pathway in cell fate specifications of MCCs and ionocytes.