Canonical WNT/beta-catenin signaling is required for ureteric branching.
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. Newborn mutant mice demonstrated bilateral renal aplasia or renal dysplasia. Analysis of the embryologic events leading to this phenotype revealed that abnormal ureteric branching at E12.5 precedes histologic abnormalities at E13.5. Microarray analysis of E12.5 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.
Bridgewater
Darren
D
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Cox
Brian
B
Cain
Jason
J
Lau
Agnes
A
Athaide
Valerie
V
Gill
Paul S
PS
Kuure
Satu
S
Sainio
Kirsi
K
Rosenblum
Norman D
ND
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007668:Kidney / Q000002:abnormalities / Q000166:cytology / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D015398:Signal Transduction; D014513:Ureter / Q000166:cytology / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051176:beta Catenin