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.