Sex-specific expression of CTNNB1 in the gonadal morphogenesis of the chicken

Seung-Min Bae,Jin-Young Lee,Jinyoung Kim,Fuller W Bazer,Gwonhwa Song,Wooyoung Jeong,Whasun Lim

doi:10.1186/1477-7827-11-89

Abstract

BackgroundBeta-catenin (CTNNB1), as a key transcriptional regulator in the WNT signal transduction cascade, plays a pivotal role in multiple biological functions such as embryonic development and homeostasis in adults. Although it has been suggested that CTNNB1 is required for gonad development and maintenance of ovarian function in mice, little is known about the expression and functional role of CTNNB1 in gonadal development and differentiation in the chicken reproductive system.MethodsTo examine sex-specific, cell-specific and temporal expression of CTNNB1 mRNA and protein during gonadal development to maturation of reproductive organs, we collected left and right gonads apart from mesonephric kidney of chicken embryos on embryonic day (E) 6, E9, E14, E18, as well as testes, oviduct and ovaries from 12-week-old and adult chickens and performed quantitative PCR, in situ hybridization, and immunohistochemical analyses. In addition, localization of Sertoli cell markers such as anti-Müllerian hormone (AMH), estrogen receptor alpha (ESR1), cyclin D1 (CCND1) and N-cadherin (CDH2) during testicular development was evaluated.ResultsResults of the present study showed that CTNNB1 mRNA and protein are expressed predominantly in the seminiferous cords on E6 to E14 in the male embryonic gonad, and are mainly localized to the medullary region of female embryonic gonads from E6 to E9. In addition, CTNNB1 mRNA and protein are abundant in the Sertoli cells in the testes and expressed predominantly in luminal epithelial cells of the oviduct, but not in the ovaries from 12-week-old and adult chickens. Concomitant with CTNNB1, AMH, ESR1, CCND1 and CDH2 were detected predominantly in the seminiferous cord of the medullary region of male gonads at E9 (after sex determination) and then maintained or decreased until hatching. Interestingly, AMH, ESR1, CCND1 and CDH2 were located in seminiferous tubules of the testes from 12-weeks-old chickens and ESR1, CCND1 and CDH2 were expressed predominantly in the Sertoli cells within seminiferous tubules of adult testes.ConclusionsCollectively, these results revealed that CTNNB1 is present in gonads of both sexes during embryonic development and it may play essential roles in differentiation of Sertoli cells during formation of seminiferous tubules during development of the testes.

Highlights

Beta-catenin (CTNNB1), as a key transcriptional regulator in the WNT signal transduction cascade, plays a pivotal role in multiple biological functions such as embryonic development and homeostasis in adults
Without WNT ligand, CTNNB1 is phosphorylated at serine residue 33 and 37 and provides a binding site for the E3 ubiquitin ligase, resulting in CTNNB1 ubiquitination and degradation by the destruction complex composed of Axin, adenomatous polyposis coli gene product (APC), glycogen synthase kinase 3 (GSK3), protein phosphatase 2A (PP2A), and casein kinase 1 (CK1) [2]
In situ hybridization analysis showed that CTNNB1 mRNA is expressed predominantly in the seminiferous cords of developing testes from embryonic day 6 (E6) to E14 (Figure 1B)

Summary

Introduction

Beta-catenin (CTNNB1), as a key transcriptional regulator in the WNT signal transduction cascade, plays a pivotal role in multiple biological functions such as embryonic development and homeostasis in adults. Beta-catenin (CTNNB1), the vertebrate homolog of Armadillo in Drosophila melanogaster, plays important roles as a transcriptional co-activator in the WNT signal transduction cascade as well as linkage of the cadherin complex to the actin filament network during early embryogenesis and adult homeostasis [1]. Without WNT ligand, CTNNB1 is phosphorylated at serine residue 33 and 37 and provides a binding site for the E3 ubiquitin ligase, resulting in CTNNB1 ubiquitination and degradation by the destruction complex composed of Axin, adenomatous polyposis coli gene product (APC), glycogen synthase kinase 3 (GSK3), protein phosphatase 2A (PP2A), and casein kinase 1 (CK1) [2]. It is well known that deregulation of the WNT/ CTNNB1 signal transduction cascade results in colorectal carcinogenesis through excessive proliferation or renewal of stem cells resulting from a CTNNB1 mutation [4]

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Discussion

Conclusion