Sex-specific roles of beta-catenin in mouse gonadal development.
Sexually dimorphic development of the gonads is controlled by positive and negative regulators produced by somatic cells. Many Wnt ligands, including ones that signal via the canonical beta-catenin pathway, are expressed in fetal gonads. beta-catenin, a key transcriptional regulator of the canonical Wnt pathway and an element of the cell adhesion complex, is essential for various aspects of embryogenesis. To study the involvement of beta-catenin in sex determination, we ablated beta-catenin specifically in the SF1-positive population of somatic cells. Although beta-catenin was present in gonads of both sexes, it was necessary only for ovarian differentiation but dispensable for testis development. Loss of beta-catenin in fetal testes did not affect Sertoli cell differentiation, testis morphogenesis or masculinization of the embryos. However, we observed molecular and morphological defects in ovaries lacking beta-catenin, including formation of testis-specific coelomic vessel, appearance of androgen-producing adrenal-like cells and loss of female germ cells. These phenotypes were strikingly similar to those found in the R-spondin1 (Rspo1) and Wnt4 knockout ovaries. In the absence of beta-catenin, expression of Wnt4 was down-regulated while that of Rspo1 was not affected, placing beta-catenin as a component in between Rspo1 and Wnt4. Our results demonstrate that beta-catenin is responsible for transducing sex-specific signals in the SF1-positive somatic cell population during mouse gonadal development.
Liu
Chia-Feng
CF
Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, 3806 VMBSB, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
Bingham
Nathan
N
Parker
Keith
K
Yao
Humphrey H-C
HH
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072260:RNA Splicing Factors; D012733:Sex Differentiation; D015398:Signal Transduction; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000072260:RNA Splicing Factors; C491514:Sf1 protein, mouse; D014157:Transcription Factors; D051176:beta Catenin