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

Kim, Alex C.; Reuter, Anne L.; Zubair, Mohamad; Else, Tobias; Serecky, Kerri; Bingham, Nathan C.; Lavery, Gareth G.; Parker, Keith L.; Hammer, Gary D.

doi:10.1242/dev.021493

Cited by 202Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationRenal and related cancers

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

Kim, Alex C., Reuter, Anne L., Zubair, Mohamad, Else, Tobias, Serecky, Kerri, Bingham, Nathan C., Lavery, Gareth G., Parker, Keith L. +1 more·2008·Development

DOI 10.1242/dev.021493

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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.

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The Wnt signaling pathway is thought to be important in the embryonic development of the adrenal gland.
“The Wnt signaling pathway is thought to be important in the embryonic development of the adrenal gland (139).”
From Adrenal incidentaloma (2020) · cites this paper as [139]
In the normal adrenal gland, the WNT/β-catenin signaling pathway plays a crucial role in both embryonic development and maintenance of the adrenal cortex.
“In the normal adrenal gland, the WNT/β-catenin signaling pathway plays a crucial role in both embryonic development and maintenance of the adrenal cortex (228).”
From Adrenocortical carcinoma (2014) · cites this paper as [228]
Conditional knockout of β-catenin in a transgenic mouse resulted in the absence of the adrenal gland at embryonic day 18.5.
“Conditional knockout of β-catenin in a transgenic mouse resulted in the absence of the adrenal gland at embryonic day 18.5.”
From Adrenocortical carcinoma (2014) · cites this paper as [228]
In mice with incomplete β-catenin knockout, at age 45 weeks postpartum, they exhibited thinned and disorganized adrenal cortex with increased apoptosis.
“In mice harboring incomplete β-catenin knockout (knockout of β-catenin in a subset of adrenocortical cells), although normal adrenal development occurred, at age 45 weeks postpartum, these mice exhibited thinned and disorganized adrenal cortex in the setting of increased apoptosis (228).”
From Adrenocortical carcinoma (2014) · cites this paper as [228]

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Authors: Kim, A. C., Reuter, A. L., Zubair, M., Else, T., Serecky, K., Bingham, N. C., Lavery, G. G., Parker, K. L., & Hammer, G. D.
Affiliations: University of Michigan (US)
The University of Texas Southwestern Medical Center (US)
Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678. USA.
Corresponding author: Hammer, Gary D.
ORCID: Kim, Alex C.
Else, Tobias
Bingham, Nathan C.
Lavery, Gareth G.
Hammer, Gary D.
Venue: Development
Publisher: The Company of Biologists
Published: 2008-08-01
Volume: 135
Issue: 15
Pages: 2593-2602
ISSN: 0950-1991 (ISSN-L)
1477-9129
DOI: 10.1242/dev.021493
OpenAlex: W2003456330
Cited by: 202
References: 48
Citations by year: 2026: 5 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 10 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 12 · 2017: 12 · 2016: 17 · 2015: 13 · 2014: 14 · 2013: 14 · 2012: 13
FWCI: 5.07
Type: journal article
Language: en
Open access: closed
Locations: Development (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK062027, DK-54480, R01DK054480, R01DK062027)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD046743, R01HD046743)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
Keywords: β-catenin, steroidogenic factor 1, adrenal cortex development, conditional gene inactivation, transcriptional coactivator
MeSH terms: Adrenal Cortex, Animals, Cell Differentiation, Signal Transduction, Biomarkers, Mice, Knockout, Gene Expression Regulation, Developmental, Integrases, Cell Proliferation, Wnt Proteins, beta Catenin, Mice, Steroidogenic Factor 1

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

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