Canonical WNT/β-catenin signaling is required for ureteric branching
Canonical WNT/β-catenin signaling is required for ureteric branching
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DOI：
10.1016/j.ydbio.2008.02.010
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发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Rosenblum, Norman D.
中科院分区：
文献类型：
--
作者：
Bridgewater, Darren;Cox, Brian;Rosenblum, Norman D.
WNT/β-连环蛋白信号传导在肾脏发育过程中的肾单位形成中具有确定的作用。然而，β-连环蛋白在体内输尿管形态发生中的作用尚不明确。我们建立了一个针对输尿管芽细胞谱系的β-连环蛋白缺乏的小鼠遗传模型。Newbom突变小鼠表现为双侧肾发育不全或肾发育不良。对导致这种表型的胚胎学事件的分析显示，在E12.5时输尿管分支异常先于E13.5时的组织学异常。E 12.5肾组织的微阵列分析确定了在异常分支阶段破坏的一小部分肾模式基因中Emx 2和Lim 1表达降低。这些改变之后是Emx 2下游基因表达的降低，包括Lim 1、Pax 2和输尿管尖端标记物c-ret和Wnt 11。总之，这些数据表明，β-连环蛋白在肾分支形态发生过程中通过控制控制输尿管分支的基因层次来执行基本功能。皇冠版权所有（C）2008由爱思唯尔公司出版。All rights reserved.
WNT/beta-catenin signaling has an established role in nephron formation during kidney development. Yet, the role of beta-catenin during ureteric morphogenesis in vivo is undefined. We generated a murine genetic model of beta-catenin deficiency targeted to the ureteric bud cell lineage. Newbom mutant mice demonstrated bilateral renal aplasia or renal dysplasia. Analysis of the embryologic events leading to this phenotype revealed that abnormal ureteric branching at E 12.5 precedes histologic abnormalities at E 13.5. Microarray analysis of E 12.5 kidney tissue identified decreased Emx2 and Lim1 expression among a small subset of renal patterning genes disrupted at the stage of abnormal branching. These alterations are followed by decreased expression of genes downstream of Emx2, including Lim1, Pax2, and the ureteric tip markers, c-ret and Wnt 11. Together, these data demonstrate that beta-catenin performs essential functions during renal branching morphogenesis via control of a hierarchy of genes that control ureteric branching. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.