BMP receptor ALK3 controls collecting system development
BMP receptor ALK3 controls collecting system development
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DOI：
10.1681/asn.2007010080
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发表时间：
2008-01-01
影响因子：
13.6
通讯作者：
Rosenblum, Norman D.
中科院分区：
文献类型：
--
作者：
Hartwig, Sunny;Bridgewater, Darren;Rosenblum, Norman D.
在肾集合系统形成过程中调控输尿管芽生长和分支的分子信号在很大程度上是不确定的。骨形态发生蛋白（BMP）家族成员通过I型BMP受体ALK 3发出信号，抑制体外输尿管芽和集合管细胞形态发生。我们通过产生局限于输尿管芽谱系的ALK 3缺乏的小鼠模型（Alk 3（UB-/-）小鼠）来研究BMP信号传导途径在体内的功能。在分支形态发生开始时，Alk（UB-/-）肾脏的特征是异常的原发性（1度）输尿管芽分支模式和输尿管芽分支数量增加。然而，在肾脏发育的后期阶段，Alk 3（UB-/-）肾脏比野生型肾脏具有更少的输尿管芽分支和集合管。出生后Alk 3（UB-/-）小鼠表现出发育不良的肾脏表型，其特征为肾髓质发育不全、髓质集合管数量减少以及髓质小管中β-连环蛋白和c-MYC表达异常。总之，正常的肾脏发育需要ALK 3依赖性BMP信号传导，其控制输尿管芽分支。
The molecular signals that regulate growth and branching of the ureteric bud during formation of the renal collecting system are largely undefined. Members of the bone morphogenetic protein (BMP) family signal through the type I BMP receptor ALK3 to inhibit ureteric bud and collecting duct cell morphogenesis in vitro. We investigated the function of the BMP signaling pathway in vivo by generating a murine model of ALK3 deficiency restricted to the ureteric bud lineage (Alk3(UB-/-) mice). At the onset of branching morphogenesis, Alk(UB-/-) kidneys are characterized by an abnormal primary (1 degrees) ureteric bud branch pattern and an increased number of ureteric bud branches. However, during later stages of renal development, Alk3(UB-/-) kidneys have fewer ureteric bud branches and collecting ducts than wild-type kidneys. Postnatal Alk3(UB-/-) mice exhibit a dysplastic renal phenotype characterized by hypoplasia of the renal medulla, a decreased number of medullary collecting ducts, and abnormal expression of beta-catenin and c-MYC in medullary tubules. In summary, normal kidney development requires ALK3-dependent BMP signaling, which controls ureteric bud branching.