期刊
DEVELOPMENT
卷 135, 期 15, 页码 2593-2602出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.021493
关键词
adrenal cortex; beta-catenin; Cre-loxP; gene knockout; steroidogenic factor 1
资金
- NICHD NIH HHS [HD 046743] Funding Source: Medline
- NIDDK NIH HHS [DK 54480, DK 062027] Funding Source: Medline
The nuclear receptor steroidogenic factor 1 (Sf1, Nr5a1) is essential for adrenal development and regulates genes that specify differentiated adrenocortical function. The transcriptional coactivator beta-catenin reportedly synergizes with Sf1 to regulate a subset of these target genes; moreover, Wnt family members, signaling via beta-catenin, are also implicated in adrenocortical development. To investigate the role of beta-catenin in the adrenal cortex, we used two Sf1/Cre transgenes to inactivate conditional beta-catenin alleles. Inactivation of beta-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 beta-catenin inactivation showed decreased proliferation in presumptive adrenocortical precursor cells. By contrast, the Sf1/Cre(low) transgene effected a lesser degree of beta-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 beta-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.
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