Targeted disruption of -catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex

The nuclear receptor steroidogenic factor 1 (Sf1, Nr5a1) is essential for adrenal development and regulates genes that specify differentiated adrenocortical function. The transcriptional coactivator -catenin reportedly synergizes with Sf1 to regulate a subset of these target genes; moreover, Wnt family members, signaling via -catenin, are also implicated in adrenocortical development. To investigate the role of -catenin in the adrenal cortex, we used two Sf1/Cre transgenes to inactivate conditional -catenin alleles. Inactivation of -catenin mediated by Sf1/Cre^high, a transgene expressed at high levels, caused adrenal aplasia in newborn mice. Analysis of fetal adrenal development with Sf1/Cre^high-mediated -catenin inactivation showed decreased proliferation in presumptive adrenocortical precursor cells. By contrast, the Sf1/Cre^low transgene effected a lesser degree of -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 -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.