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Background  Establishment and maintenance of a functional central nervous system (CNS) requires a highly orchestrated process of neural progenitor cell proliferation, cell cycle exit, and differentiation. An evolutionary conserved program consisting of Notch signalling mediated by basic Helix-Loop-Helix (bHLH) transcription factor activity is necessary for both the maintenance of neural progenitor cell character and the progression of neurogenesis; however, additional players in mammalian CNS neural specification remain largely unknown. In  Drosophila  we recently characterized Hamlet, a transcription factor that mediates Notch signalling and neural cell fate.    Methodology/Principal Findings  Hamlet is a member of the Prdm (PRDI-BF1 and RIZ homology domain containing) proto-oncogene transcription factor family, and in this study we report that multiple genes in the  Prdm  family ( Prdm6 ,  8 ,  12 ,  13  and  16 ) are expressed in the developing mouse CNS in a spatially and temporally restricted manner. In developing spinal cord  Prdm8, 12  and  13  are expressed in precise neuronal progenitor zones suggesting that they may specify discrete neuronal subtypes. In developing telencephalon  Prdm12  and  16  are expressed in the ventricular zone in a lateral to medial graded manner, and  Prdm8  is expressed in a complementary domain in postmitotic neurons. In postnatal brain  Prdm8  additionally shows restricted expression in cortical layers 2/3 and 4, the hippocampus, and the amygdala. To further elucidate roles of  Prdm8  and  16  in the developing telencephalon we analyzed the relationship between these factors and the bHLH Hes (Hairy and enhancer of split homolog) effectors of Notch signalling. In  Hes  null telencephalon neural differentiation is enhanced,  Prdm8  expression is upregulated, and  Prdm16  expression is downregulated; conversely  in utero  electroporation of  Hes1  into the developing telencephalon upregulates  Prdm16  expression.    Conclusions/Significance  Our data demonstrate that  Prdm  genes are regulated by the Notch-Hes pathway and represent strong candidates to control neural class specification and the sequential progression of mammalian CNS neurogenesis.

Prdm Proto-Oncogene Transcription Factor Family Expression and Interaction with the Notch-Hes Pathway in Mouse Neurogenesis