Msx1 and Msx2 promote meiosis initiation

• DOI: 10.1242/dev.068452
• Publication Date: 2011-11-10T07:20:51Z
• Authors: Ronan Le Bouffant; Benoit Souquet; Nathalie Duval; Clotilde Duquenne; Roxane Hervé; Nelly Frydman; Benoit Robert; René Habert; Gabriel Livera
• Keywords: 0301 basic medicine; Mouse; [SDV]Life Sciences [q-bio]; Tretinoin; Mice; 03 medical and health sciences; Organ Culture Techniques; Cell Line, Tumor; Germ cells; Animals; Humans; Adaptor Proteins, Signal Transducing; Homeodomain Proteins; MSX1 Transcription Factor; Foetal ovary; 0303 health sciences; Ovary; Gene Expression Regulation, Developmental; Proteins; Foetal ovary Germ cells Msx Mouse Human; Msx; Meiosis; Bone Morphogenetic Proteins; Mutation; Female; Human

The mechanisms regulating germ line sex determination and meiosis initiation are poorly understood. Here, we provide evidence for the involvement of homeobox Msx transcription factors in foetal meiosis initiation in mammalian germ cells. Upon meiosis initiation, Msx1 and Msx2 genes are strongly expressed in the foetal ovary, possibly stimulated by soluble factors found there: bone morphogenetic proteins Bmp2 and Bmp4, and retinoic acid. Analysis of Msx1/Msx2 double mutant embryos revealed a majority of undifferentiated germ cells remaining in the ovary and, importantly, a decrease in the number of meiotic cells. In vivo, the Msx1/Msx2 double-null mutation prevented full activation of Stra8, a gene required for meiosis. In F9 cells, Msx1 can bind to Stra8 regulatory sequences and Msx1 overexpression stimulates Stra8 transcription. Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line.