Canonical WNT/β-catenin signaling is required for ureteric branching

被引：119

作者：

Bridgewater, Darren ^{[1
,5
]}

Cox, Brian ^{[5
]}

Cain, Jason ^{[1
,5
]}

Lau, Agnes ^{[5
]}

Athaide, Valerie ^{[5
]}

Gill, Paul S. ^{[3
,4
,5
]}

Kuure, Satu ^{[2
]}

Sainio, Kirsi ^{[2
]}

Rosenblum, Norman D. ^{[1
,3
,4
,5
]}

机构：

[1] Hosp Sick Children, Div Nephrol, Toronto, ON M5G 1X8, Canada

[2] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland

[3] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A1, Canada

[4] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada

[5] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada

来源：

DEVELOPMENTAL BIOLOGY | 2008年 / 317卷 / 01期

关键词：

beta-catenin; kidney development; branching morphogenesis; WNT signaling; canonical signaling; microarray; Emx2;

D O I：

10.1016/j.ydbio.2008.02.010

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：83 / 94

页数：12

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