Testis determination requires insulin receptor family function in mice

Serge Nef, Sunita Verma-Kurvari, Jussi Merenmies, Jean Dominique Vassalli, Argiris Efstratiadis, Domenico Accili, Luis F. Parada

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

In mice, gonads are formed shortly before embryonic day 10.5 by the thickening of the mesonephros and consist of somatic cells and migratory primordial germ cells. The male sex-determining process is set in motion by the sex-determining region of the Y chromosome (Sry), which triggers differentiation of the Sertoli cell lineage. In turn, Sertoli cells function as organizing centres and direct differentiation of the testis. In the absence of Sry expression, neither XX nor XY gonads develop testes, and alterations in Sry expression are often associated with abnormal sexual differentiation. The molecular signalling mechanisms by which Sry specifies the male pathway and models the undifferentiated gonad are unknown. Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igflr and Irr, is required for the appearance of male gonads and thus for male sexual differentiation. XY mice that are mutant for all three receptors develop ovaries and show a completely female phenotype. Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination.

Original languageEnglish (US)
Pages (from-to)291-295
Number of pages5
JournalNature
Volume426
Issue number6964
DOIs
StatePublished - Nov 20 2003

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Insulin Receptor
Gonads
Testis
Sex Differentiation
Sertoli Cells
Mesonephros
Y Chromosome
Cell Lineage
Germ Cells
Ovary
Insulin
Phenotype

ASJC Scopus subject areas

  • General

Cite this

Nef, S., Verma-Kurvari, S., Merenmies, J., Vassalli, J. D., Efstratiadis, A., Accili, D., & Parada, L. F. (2003). Testis determination requires insulin receptor family function in mice. Nature, 426(6964), 291-295. https://doi.org/10.1038/nature02059

Testis determination requires insulin receptor family function in mice. / Nef, Serge; Verma-Kurvari, Sunita; Merenmies, Jussi; Vassalli, Jean Dominique; Efstratiadis, Argiris; Accili, Domenico; Parada, Luis F.

In: Nature, Vol. 426, No. 6964, 20.11.2003, p. 291-295.

Research output: Contribution to journalArticle

Nef, S, Verma-Kurvari, S, Merenmies, J, Vassalli, JD, Efstratiadis, A, Accili, D & Parada, LF 2003, 'Testis determination requires insulin receptor family function in mice', Nature, vol. 426, no. 6964, pp. 291-295. https://doi.org/10.1038/nature02059
Nef S, Verma-Kurvari S, Merenmies J, Vassalli JD, Efstratiadis A, Accili D et al. Testis determination requires insulin receptor family function in mice. Nature. 2003 Nov 20;426(6964):291-295. https://doi.org/10.1038/nature02059
Nef, Serge ; Verma-Kurvari, Sunita ; Merenmies, Jussi ; Vassalli, Jean Dominique ; Efstratiadis, Argiris ; Accili, Domenico ; Parada, Luis F. / Testis determination requires insulin receptor family function in mice. In: Nature. 2003 ; Vol. 426, No. 6964. pp. 291-295.
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