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First published online 3 July 2008
doi: 10.1242/dev.021493

Development 135, 2593-2602 (2008)
Published by The Company of Biologists 2008
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Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex

Alex C. Kim1,*, Anne L. Reuter2,*, Mohamad Zubair2, Tobias Else1, Kerri Serecky1, Nathan C. Bingham2, Gareth G. Lavery2, Keith L. Parker2 and Gary D. Hammer1,{dagger}

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.

{dagger} Author for correspondence (e-mail: ghammer{at}umich.edu)

Accepted 28 May 2008

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 of β-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.

Key words: Adrenal cortex, β-Catenin, Cre-loxP, Gene knockout, Steroidogenic factor 1






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