SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site
SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site
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DOI：
10.1016/s1534-5807(04)00108-x
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发表时间：
2004-05-01
影响因子：
11.8
通讯作者：
Martin, GR
中科院分区：
文献类型：
--
作者：
Grieshammer, U;Ma, L;Martin, GR
肾脏发育发生在沿体轴沿着的固定位置。当邻近的肾间质分泌GDNF时，单个输尿管芽从肾导管中出现。GDNF表达的后部限制被认为是输尿管芽发育的正确定位的关键。在这里，我们表明，小鼠突变体缺乏SLIT 2或其受体ROBO 2，分子已知的主要功能在轴突的指导和细胞迁移，发展多余的输尿管芽，仍然不适当地连接到肾小管，和SLIT 2/ROBO 2信号转导的肾间充质。此外，我们表明，GDNF表达不适当地维持在这些突变体的前肾间充质。因此，我们的数据确定了一个细胞间信号传导系统，直接或间接地限制了GDNF表达域的范围，从而精确地定位了肾脏诱导的位点。
Kidney development occurs in a stereotypic position along the body axis. It begins when a single ureteric bud emerges from the nephric duct in response to GDNF secreted by the adjacent nephrogenic mesenchyme. Posterior restriction of Gdnf expression is considered critical for, correct positioning of ureteric bud development. Here we show that mouse mutants lacking either SLIT2 or its receptor ROBO2, molecules known primarily for their function in axon guidance and cell migration, develop supernumerary ureteric buds that remain inappropriately connected to the nephric duct, and that the SLIT2/ROBO2 signal is transduced in the nephrogenic mesenchyme. Furthermore, we show that Gdnf expression is inappropriately maintained in anterior nephrogenic mesenchyme in these mutants. Thus our data identify an intercellular signaling system that restricts, directly or indirectly, the extent of the Gdnf expression domain, thereby precisely positioning the site of kidney induction.