Notch regulates cell fate in the developing pronephros
Notch regulates cell fate in the developing pronephros
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DOI：
10.1006/dbio.2000.9913
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发表时间：
2000-11-15
影响因子：
2.7
通讯作者：
Mercola, M
中科院分区：
文献类型：
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作者：
McLaughlin, KA;Rones, MS;Mercola, M
原肾内调节细胞命运的机制尚不清楚，但对泌尿生殖系统的后续发育很重要，并且与终肾的肾形成有许多相似之处。Notch-1、serate -1和Delta-1在爪蟾发育过程中的动态表达提示该通路在细胞命运分离中起作用。Notch-1或RBP-J/Su(H)蛋白的条件活性形式对Notch信号的失活会阻止正常的导管形成和导管细胞分化遗传标记的适当表达。抑制内源性Notch信号则会产生相反的效果。结合mRNA的表达模式，这些数据表明内源性Notch信号可以抑制血管背前区（细胞通常注定要形成小管）的导管分化。此外，肾原血管中Notch信号的升高既扰乱了分化小管网络的特征模式，又增加了肾原前细胞早期标志物Pax-e和Wilms肿瘤抑制基因（wt - 1）的表达。我们提出Notch信号在导管和小管细胞命运的早期选择以及随后控制小管细胞的模式和发育中起着以前未被认识到的作用。(C) 2000年学术出版社。
The mechanisms that regulate cell fate within the pronephros are poorly understood but are important for the subsequent development of the urogenital system and show many similarities to nephrogenesis in the definitive kidney. Dynamic expression of Notch-1, Serrate-1, and Delta-1 in the developing Xenopus pronephros suggests a role for this pathway in cell fate segregation. Misactivation of Notch signaling using conditionally active forms of either Notch-1 or RBP-J/Su(H) proteins prevented normal duct formation and the proper expression of genetic markers of duct cell differentiation. Inhibition of endogenous Notch signaling elicited the opposite effect. Taken together with the mRNA expression patterns, these data suggest that endogenous Notch signaling functions to inhibit duct differentiation in the dorsoanterior region of the anlage where cells are normally fated to form tubules. In addition, elevated Notch signaling in the pronephric anlage both perturbed the characteristic pattern of the differentiated tubule network and increased the expression of early markers of pronephric precursor cells, Pax-e and Wilms' tumor suppressor gene (Wt-l). We propose that Notch signaling plays a previously unrecognized role in the early selection of duct and tubule cell fates as well as functioning subsequently to control tubule cell patterning and development. (C) 2000 Academic Press.