Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1
Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1
复制标题
DOI：
10.1016/j.ydbio.2006.08.051
复制
发表时间：
2006-11-15
影响因子：
2.7
通讯作者：
Licht, Jonathan D.
中科院分区：
文献类型：
--
作者：
Basson, M. Albert;Watson-Johnson, Judy;Licht, Jonathan D.
输尿管芽状上皮细胞的分支是形成肾脏发育的关键形态发生过程。胶质细胞源性神经营养因子(GDNF)启动输尿管芽的形成，并促进随后的分支形态发生。GDNF如何协调分支形态发生尚不清楚。在这里，我们表明，缺乏受体酪氨酸激酶拮抗剂Sprouty I(Spry1)导致不规则的分支形态发生，其特征是输尿管芽尖的数量和大小都增加了。在上皮中特异性地缺失Spry]与上皮性Wnt11表达增加以及间充质GDNF表达增加有关。我们认为，Spry]调控GDNF/Ret/Wnt11-正反馈环，在分支形态发生过程中协调间充质-上皮对话。基因实验表明，在整个肾脏发育过程中，积极信号(GDNF)和抑制信号(Sprouty1)必须保持良好的平衡，以防止发育不良或囊性增生。在Spry1基因缺失的肾脏中会出现上皮囊肿，这与在人类疾病中观察到的一些分子特征相似，这表明Spry1基因缺失的小鼠可能是囊性增生的有用动物模型。(C)2006 Elsevier Inc.保留所有权利。
Branching of ureteric bud-derived epithelia] tubes is a key morphogenetic process that shapes development of the kidney. Glial cell line-derived neurotrophic factor (GDNF) initiates ureteric bud formation and promotes subsequent branching morphogenesis. Exactly how GDNF coordinates branching morphogenesis is unclear. Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty I (Spry1) results in irregular branching morphogenesis characterized by both increased number and size of ureteric bud tips. Deletion of Spry] specifically in the epithelium is associated with increased epithelial Wnt11 expression as well as increased mesenchymal Gdnf expression. We propose that Spry] regulates a Gdnf/Ret/Wnt11-positive feedback loop that coordinates mesenchymal-epithelial dialogue during branching morphogenesis. Genetic experiments indicate that the positive (GDNF) and inhibitory (Sprouty1) signals have to be finely balanced throughout renal development to prevent hypoplasia or cystic hyperplasia. Epithelial cysts develop in Spry1-deficient kidneys that share several molecular characteristics with those observed in human disease, suggesting that Spry1 null mice may be useful animal models for cystic hyperplasia. (c) 2006 Elsevier Inc. All rights reserved.