Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex
Author:
Kim Alex C.1, Reuter Anne L.2, Zubair Mohamad2, Else Tobias1, Serecky Kerri1, Bingham Nathan C.2, Lavery Gareth G.2, Parker Keith L.2, Hammer Gary D.1
Affiliation:
1. Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678. USA. 2. Departments of Internal Medicine and Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390-8857, USA.
Abstract
The nuclear receptor steroidogenic factor 1 (Sf1, Nr5a1) is essential for adrenal development and regulates genes that specify differentiated adrenocortical function. The transcriptional coactivator β-catenin reportedly synergizes with Sf1 to regulate a subset of these target genes;moreover, Wnt family members, signaling via β-catenin, are also implicated in adrenocortical development. To investigate the role ofβ-catenin in the adrenal cortex, we used two Sf1/Cre transgenes to inactivate conditional β-catenin alleles. Inactivation of β-catenin mediated by Sf1/Crehigh, a transgene expressed at high levels, caused adrenal aplasia in newborn mice. Analysis of fetal adrenal development with Sf1/Crehigh-mediated β-catenin inactivation showed decreased proliferation in presumptive adrenocortical precursor cells. By contrast, the Sf1/Crelow transgene effected a lesser degree of β-catenin inactivation that did not affect all adrenocortical cells, permitting adrenal survival to reveal age-dependent degeneration of the cortex. These results define crucial roles for β-catenin - presumably as part of the Wnt canonical signaling pathway - in both embryonic development of the adrenal cortex and in maintenance of the adult organ.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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