Journal article
The Mammalian Doublesex Homolog DMRT1 Is a Transcriptional Gatekeeper that Controls the Mitosis versus Meiosis Decision in Male Germ Cells
Developmental cell, Vol.19(4), pp.612-624
10/19/2010
Handle:
https://hdl.handle.net/2376/106472
PMCID: PMC2996490
PMID: 20951351
Abstract
The switch from mitosis to meiosis is a unique feature of germ cell development. In mammals, meiotic initiation requires retinoic acid (RA), which activates meiotic inducers, including Stra8, but how the switch to meiosis is controlled in male germ cells (spermatogonia) remains poorly understood. Here we examine the role of the Doublesex-related transcription factor DMRT1 in adult spermatogenesis using conditional gene targeting in the mouse. Loss of Dmrt1 causes spermatogonia to precociously exit the spermatogonial program and enter meiosis. Therefore, DMRT1 determines whether male germ cells undergo mitosis and spermatogonial differentiation or meiosis. Loss of Dmrt1 in spermatogonia also disrupts cyclical gene expression in Sertoli cells. DMRT1 acts in spermatogonia to restrict RA responsiveness, directly repress Stra8 transcription, and activate transcription of the spermatogonial differentiation factor Sohlh1, thereby preventing meiosis and promoting spermatogonial development. By coordinating spermatogonial development and mitotic amplification with meiosis, DMRT1 allows abundant, continuous production of sperm.
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► Loss of Dmrt1 causes spermatogonia to precociously enter meiosis ► DMRT1 restricts retinoic acid responsiveness and directly represses Stra8 ► DMRT1 promotes spermatogonial differentiation ► DMRT1 coordinates mitotis and meiosis to allow abundant spermatogenesis
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Details
- Title
- The Mammalian Doublesex Homolog DMRT1 Is a Transcriptional Gatekeeper that Controls the Mitosis versus Meiosis Decision in Male Germ Cells
- Creators
- Clinton K Matson - Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USAMark W Murphy - Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USAMichael D Griswold - School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USAShosei Yoshida - Division of Germ Cell Biology, National Institute of Basic Biology, and Department of Basic Biology, SOKENDAI, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, JapanVivian J Bardwell - Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USADavid Zarkower - Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA
- Publication Details
- Developmental cell, Vol.19(4), pp.612-624
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547095001842
- Language
- English
- Resource Type
- Journal article