Costantini Frank, Shakya Reena
Department of Genetics and Development, Columbia University Medical Center, New York 10032, USA.
Bioessays. 2006 Feb;28(2):117-27. doi: 10.1002/bies.20357.
Signaling by GDNF through the Ret receptor is required for normal growth of the ureteric bud during kidney development. However, the precise role of GDNF/Ret signaling in renal branching morphogenesis and the specific responses of ureteric bud cells to GDNF remain unclear. Recent studies have provided new insight into these issues. The localized expression of GDNF by the metanephric mesenchyme, together with several types of negative regulation, is important to elicit and correctly position the initial budding event from the Wolffian duct. GDNF also promotes the continued branching of the ureteric bud. However, it does not provide the positional information required to specify the pattern of ureteric bud growth and branching, as its site of synthesis can be drastically altered with minimal effects on kidney development. Cells that lack Ret are unable to contribute to the tip of the ureteric bud, apparently because GDNF-driven proliferation is required for the formation and growth of this specialized epithelial domain.
在肾脏发育过程中，胶质细胞源性神经营养因子（GDNF）通过Ret受体发出的信号对于输尿管芽的正常生长是必需的。然而，GDNF/Ret信号在肾脏分支形态发生中的精确作用以及输尿管芽细胞对GDNF的特异性反应仍不清楚。最近的研究为这些问题提供了新的见解。后肾间充质中GDNF的局部表达，连同几种类型的负调控，对于引发并正确定位来自 Wolffian 管的初始出芽事件很重要。GDNF 还促进输尿管芽的持续分支。然而，它并不提供指定输尿管芽生长和分支模式所需的位置信息，因为其合成位点可以发生剧烈改变，而对肾脏发育的影响最小。缺乏Ret的细胞无法参与输尿管芽的尖端形成，显然是因为GDNF驱动的增殖是这个特殊上皮结构域形成和生长所必需的。
