Targeted disruption of beta-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 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.
Kim
Alex C
AC
Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678. USA.
Reuter
Anne L
AL
Zubair
Mohamad
M
Else
Tobias
T
Serecky
Kerri
K
Bingham
Nathan C
NC
Lavery
Gareth G
GG
Parker
Keith L
KL
Hammer
Gary D
GD
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*
D015415:Biomarkers; D054339:Steroidogenic Factor 1; D051153:Wnt Proteins; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases