title: Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex.
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 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.
authors.affiliation: Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678. USA.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Kim
authors.forename: Anne L
authors.initials: AL
authors.lastname: Reuter
authors.forename: Mohamad
authors.initials: M
authors.lastname: Zubair
authors.forename: Tobias
authors.initials: T
authors.lastname: Else
authors.forename: Kerri
authors.initials: K
authors.lastname: Serecky
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Bingham
authors.forename: Gareth G
authors.initials: GG
authors.lastname: Lavery
authors.forename: Keith L
authors.initials: KL
authors.lastname: Parker
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hammer
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D054339:Steroidogenic Factor 1; D051153:Wnt Proteins; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases