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To beta or not to beta: canonical beta-catenin signaling pathway and ovarian development - PubMed

Review

To beta or not to beta: canonical beta-catenin signaling pathway and ovarian development

Sergei G Tevosian et al. Dev Dyn. 2008 Dec.

Abstract

The mammalian embryonic gonad is a unique organ primordium in that it can adopt two different developmental fates-namely, differentiate as either a testis or an ovary-with dramatic consequences for an individual. While a molecular cascade culminating in testis development is well characterized, the ovarian pathways still remain enigmatic. The canonical Wnt/beta-catenin signaling implements a conserved mechanism of regulating gene expression that is integral to development of all metazoans. In this review, we summarize the recent evidence that suggests a central role for this signaling pathway in the development of the mammalian female.

(c) 2008 Wiley-Liss, Inc.

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Figures

Fig. 1
Fig. 1

The canonical Wnt/β-catenin pathway (modified after (Benchabane and Ahmed, 2008)). (A). The default “off-state”. In the absence of a Wnt ligand, cytoplasmic β-catenin is constitutively engaged by a group of proteins termed “the destruction complex” containing the Axin and Adenomatous Polyposis Coli (APC) proteins. By recruiting the kinases, Casein Kinase 1α and GSK-3β, the destruction complex facilitates the phosphorylation of β-catenin. The phosphorylated β-catenin serves as a substrate for the β-Trcp E3 ubiquitin ligase that targets it for ubiquitination and proteasome-mediated degradation. (B). The “on-state”. The signaling is initiated by WNT ligand binding to Frizzled (Fz) and LRP5/6 co-receptors ultimately leading to the inhibition of the destruction complex and β̃catenin protein stabilization and entry into the nucleus. Nuclear β-catenin binding to T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription factors leads to the activation of target gene expression. The RSPO1 protein is thought to facilitate Wnt-Fz-LRP complex formation through fending off a secreted inhibitor, DKK1 (C). The regulated “off-state”. DKK1 binding to the LRP6 co-receptor blocks Wnt signal transduction by preventing formation of the Wnt-Fz-LRP6 signaling complex.

Fig. 2
Fig. 2

The canonical Wnt/β- catenin pathway is active in the embryonic ovaries but not the testes. The gonads from the embryos carrying an Axin2lacZ allele were stained for β-galactosidase (lacZ) expression. The samples (13.5dpc) are oriented with the anterior end towards the left; the gonad (g) and the mesonephros (a segmentally organized structure that serves as a base for the gonad and a duct system, m) are separated by the dotted line. The downstream target of the canonical β-catenin pathway, Axin2, is expressed in the ovary (B) and not the testis (A).

Fig. 3
Fig. 3

Sexual differentiation in mammals is driven by the opposing antagonistic activities of the transcriptional regulatory proteins: SOX9 in males and β-catenin/TCF/LEF in females.

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