Sex determination in mice

Genetics of sex determination and fertility in mammals.
In mammals, the pivotal decision to develop as male or female begins with the differentiation of the bipotential gonad allowing the development of two highly specialized organs: the testis or the ovary. In addition the gonad is the siege of germ cells differentiation that insures the propagation of species. It is now clear that the fate of the gonad and germ cells are closely linked, however, cellular and molecular mechanisms leading to somatic or germ cell differentiation are still not fully understood. Our aim is to contribute to unravelling these mechanisms involved in normal and pathologic development of testes and ovaries.

Male development : testicular differentiation.
Sexual differentiation is determined by the paternal transmission of the SRY gene located on the Y chromosome. The expression of Sry promotes testicular differentiation by up-regulation of the transcription factor Sox9. However, using mice models, we have shown that testicular differentiation can occur in the absence of Sry and Sox9 expression. The identification of these new genes is of great importance to understand how sex determination occurs in other vertebrate in which Sry and Sox9 have been shown not to be the sex determining factors. New potential sexual determinants are under investigation in our lab.

 

Female development : ovarian differentiation.
R-spondins genes (RSPO) are activators of WNT/beta-catenin signaling pathway and regulate various developmental processes and proliferation of transiently amplifying stem cells. Mutations of RSPO1 are responsible of female-to-male sex reversal and/or ovarian carcinomas predisposition indicating that Rspo1 controls ovarian differentiation. In addition, Rspo1/beta-catenin signaling pathway is also required for proliferation of germ cells and their commitment to meiosis. The different functions of the Rspo1/beta-catenin signalling pathway in sex determination and fertility are deciphered in our lab using mouse models.

 

Last publications

Steroidogenic organ development and homeostasis: A WT1-centric view. - 2015 - Molecular and cellular endocrinology - Bandiera R, Sacco S, Vidal VP, Chaboissier MC, and Schedl,A

R-spondin1 deficiency enhances β-Cell neogenesis in a murine model of diabetes. - 2014 - Pancreas - 43 P93-102 - Chahal JK, Wong VS, Chaboissier MC, and Brubaker,PL

Marker genes identify three somatic cell types in the fetal mouse ovary. - 2014 - Developmental biology - 394 P242-52 - Rastetter RH, Bernard P, Palmer JS, Chassot AA, Chen H, Western PS, Ramsay RG, Chaboissier MC, and Wilhelm,D

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation. - 2014 - Reproduction (Cambridge, England) - 148 PR97-110 - Chassot AA, Gillot I, and Chaboissier,MC

Disruption of mitotic arrest precedes precocious differentiation and transdifferentiation of pregranulosa cells in the perinatal Wnt4 mutant ovary. - 2013 - Dev Biol - Maatouk DM, Mork L, Chassot AA, Chaboissier MC, and Capel,B

WNT4 and RSPO1 together are required for cell proliferation in the early mouse gonad. - 2012 - Development - Chassot AA, Bradford ST, Auguste A, Gregoire EP, Pailhoux E, de Rooij DG, Schedl A, and Chaboissier,MC

Testicular Differentiation Occurs in Absence of R-spondin1 and Sox9 in Mouse Sex Reversals. - 2012 - PLoS Genet - 8 Pe1003170 - Lavery R, Chassot AA, Pauper E, Gregoire EP, Klopfenstein M, de Rooij DG, Mark M, Schedl A, Ghyselinck NB, and Chaboissier,MC

Loss of R-spondin1 and Foxl2 amplifies female-to-male sex reversal in XX mice. - 2011 - Sex Dev - 5 P304-17 - Auguste A, Chassot AA, Grégoire EP, Renault L, Pannetier M, Treier M, Pailhoux E, and Chaboissier,MC

β-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. - 2011 - PLoS One - 6 Pe25641 - Chassot AA, Gregoire EP, Lavery R, Taketo MM, de Rooij DG, Adams IR, and Chaboissier,MC

R-spondin1 deficiency in mice improves glycaemic control in association with increased beta cell mass. - 2011 - Diabetologia - 54 P1726-34 - Wong VS, Oh AH, Chassot AA, Chaboissier MC, and Brubaker,PL

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Chaboissier Marie-Christine
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