Ret-Dependent Cell Rearrangements in the Wolffian Duct Epithelium Initiate Ureteric Bud Morphogenesis
Ret-Dependent Cell Rearrangements in the Wolffian Duct Epithelium Initiate Ureteric Bud Morphogenesis
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DOI：
10.1016/j.devcel.2009.07.013
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发表时间：
2009-08-18
影响因子：
11.8
通讯作者：
Costantini, Frank
中科院分区：
文献类型：
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作者：
Chi, Xuan;Michos, Odysse;Costantini, Frank
虽然肾分支形态发生的遗传控制已被广泛描述，但这一过程的细胞基础仍不清楚。GDNF/RET信号传导是输尿管和肾脏发育所必需的，并且缺乏Ret的细胞被排除在嵌合肾脏中的分支输尿管芽的尖端之外。在这里，我们发现，这种排除的结果从早期视网膜依赖性细胞重排的尾侧沃尔夫管，产生一个专门的上皮结构域，后来出现的初级输尿管芽的尖端。通过将RET活性升高或降低的细胞并置，我们发现Wolffian管细胞基于RET信号传导水平竞争，以促进该域。与此同时，尾侧Wolffian管从单纯上皮短暂转化为假复层上皮，这一过程不需要Ret。因此，视网膜依赖的细胞运动和视网膜非依赖性的变化在沃尔夫管上皮有助于输尿管芽的形成。
While the genetic control of renal branching morphogenesis has been extensively described, the cellular basis of this process remains obscure. GDNF/RET signaling is required for ureter and kidney development, and cells lacking Ret are excluded from the tips of the branching ureteric bud in chimeric kidneys. Here, we find that this exclusion results from earlier Ret-dependent cell rearrangements in the caudal Wolffian duct, which generate a specialized epithelial domain that later emerges as the tip of the primary ureteric bud. By juxtaposing cells with elevated or reduced RET activity, we find that Wolffian duct cells compete, based on RET signaling levels, to contribute to this domain. At the same time, the caudal Wolffian duct transiently converts from a simple to a pseudostratified epithelium, a process that does not require Ret. Thus, both Ret-dependent cell movements and Ret-independent changes in the Wolffian duct epithelium contribute to ureteric bud formation.