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The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast.sup.1. Induction requires BMP4 signalling to prospective PGCs.sup.2 and the intrinsic action of PGC transcription factors.sup.3-6. However, the molecular mechanisms that connect BMP4 to induction of the PGC transcription factors that are responsible for segregating PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Downregulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro markedly increases the efficiency of PGC-like cell differentiation and prolongs the period of PGC competence. In the absence of Otx2 activity, differentiation of PGC-like cells becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC transcription factor BLIMP1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that OTX2 functions repressively upstream of PGC transcription factors, acting as a roadblock to limit entry of epiblast cells to the germline to a small window in space and time, thereby ensuring correct numerical segregation of germline cells from the soma.The transcription factor OTX2 ensures that germline induction is initially kept in check and only proceeds after OTX2 downregulation., Author(s): Jingchao Zhang [sup.1] , Man Zhang [sup.1] , Dario Acampora [sup.2] , Matús Vojtek [sup.1] , Detian Yuan [sup.3] , Antonio Simeone [sup.2] , Ian Chambers [sup.1] Author Affiliations:(1) [...]

Two homeobox genes, Otx1 and Otx2, act with two other previously identified homeobox genes, Emx1 and Emx2, to control development of the rostral brain in mice and are homologous with orthodenticle and empty spiracle genes in Drosophila. Thus some vertebrate and invertebrate homeobox genes are now known to be homologues. The four genes govern expression of several regions of the brain including the telencephalon. The genes' expression domains progress in the sequence Emx1, Emx2, Otx1 and Otx2.