DMRT1 prevents female reprogramming in the postnatal mammalian testis

Clinton K Matson; Mark W Murphy; Aaron L Sarver; Michael D Griswold; Vivian J Bardwell; David Zarkower

doi:10.1038/nature10239

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DMRT1 prevents female reprogramming in the postnatal mammalian testis

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DMRT1 prevents female reprogramming in the postnatal mammalian testis

Clinton K Matson, Mark W Murphy, Aaron L Sarver, Michael D Griswold, Vivian J Bardwell and David Zarkower

Nature (London), Vol.476(7358), pp.101-104

08/04/2011

DOI: https://doi.org/10.1038/nature10239

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https://hdl.handle.net/2376/112595

PMCID: PMC3150961

PMID: 21775990

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Abstract

Sex in mammals is determined in the foetal gonad by the presence or absence of the Y chromosome gene Sry , which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells 1 . This pivotal decision in a single gonadal cell type ultimately controls sexual differentiation throughout the body. Sex determination can be viewed as a battle for primacy in the foetal gonad between a male regulatory gene network in which Sry activates Sox9 and a female network involving Wnt/β-catenin signaling ( Supplemental Fig. 1 ) 2 . In females the primary sex-determining decision is not final: loss of the FOXL2 transcription factor in adult granulosa cells can reprogramme granulosa cells into Sertoli cells 2 . Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor 3 in mouse Sertoli cells, even in adults, activates Foxl2 and reprogrammes Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced, and germ cells appear feminized. Thus Dmrt1 is essential to maintain mammalian testis determination, and competing regulatory networks maintain gonadal sex long after the foetal choice between male and female. Dmrt1 and Foxl2 are conserved throughout vertebrates 4 , 5 and Dmrt1 -related sexual regulators are conserved throughout metazoans 3 . Antagonism between Dmrt1 and Foxl2 for control of gonadal sex may therefore extend beyond mammals. Reprogramming due to loss of Dmrt1 also may help explain the etiology of human syndromes linked to DMRT1 , including disorders of sexual differentiation 6 and testicular cancer 7 .

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Title: DMRT1 prevents female reprogramming in the postnatal mammalian testis
Creators: Clinton K Matson - Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA
Mark W Murphy - Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA
Aaron L Sarver - University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA
Michael D Griswold - School of Molecular Biosciences, Washington State University, Pullman, WA, USA
Vivian J Bardwell - Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA
David Zarkower - Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA
Publication Details: Nature (London), Vol.476(7358), pp.101-104
Academic Unit: Molecular Biosciences, School of
Identifiers: 99900547597201842
Language: English
Resource Type: Journal article