title: Msx1 and Msx2 promote meiosis initiation.
abstract: 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.
authors: CEA, DSV/iRCM/SCSR/LDG, Laboratoire de Développement des Gonades, Unité Cellules Souches et Radiation, F-92265 Fontenay aux Roses, France.
authors: Ronan
authors: R
authors: Le Bouffant
authors: Benoit
authors: B
authors: Souquet
authors: Nathalie
authors: N
authors: Duval
authors: Clotilde
authors: C
authors: Duquenne
authors: Roxane
authors: R
authors: Hervé
authors: Nelly
authors: N
authors: Frydman
authors: Benoit
authors: B
authors: Robert
authors: René
authors: R
authors: Habert
authors: Gabriel
authors: G
authors: Livera
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009924:Organ Culture Techniques; D010053:Ovary / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; C484084:Msx1 protein, mouse; D011506:Proteins; C484447:STRA8 protein, human; C102019:Stra8 protein, mouse; D014212:Tretinoin