Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex
Open Access
- 1 August 2008
- journal article
- Published by The Company of Biologists in Development
- Vol. 135 (15), 2593-2602
- https://doi.org/10.1242/dev.021493
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.Keywords
This publication has 42 references indexed in Scilit:
- Increased Steroidogenic Factor-1 Dosage Triggers Adrenocortical Cell Proliferation and CancerMolecular Endocrinology, 2007
- Epithelial Stem Cells: Turning over New LeavesCell, 2007
- Development of a steroidogenic factor 1/Cre transgenic mouse linegenesis, 2006
- Genetic analysis of adrenal absence: agenesis and aplasiaTrends in Endocrinology & Metabolism, 2005
- Pancreas-Specific Deletion of β-Catenin Reveals Wnt-Dependent and Wnt-Independent Functions during DevelopmentCurrent Biology, 2005
- Differential Requirement for Steroidogenic Factor-1 Gene Dosage in Adrenal Development Versus Endocrine FunctionMolecular Endocrinology, 2004
- Steroidogenic Factor-1 Is Essential for Compensatory Adrenal Growth Following Unilateral AdrenalectomyEndocrinology, 2002
- Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activatorNature Genetics, 2001
- Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress responseProceedings of the National Academy of Sciences of the United States of America, 2000
- Molecular Control of Cell Fate in the Neural Crest: The Sympathoadrenal LineageAnnual Review of Neuroscience, 1993