Evidence that helix-loop-helix proteins collaborate with retinoblastoma tumor suppressor protein to regulate cortical neurogenesis

The retinoblastoma tumor suppressor protein (pRb) family is essential for c ortical progenitors to exit the cell cycle and survive. In this report, we test the hypothesis that pRb collaborates with basic helix-loop-helix (bHLH ) transcription factors to regulate cortical neurogenesis, taking advantage of the naturally occurring dominant-inhibitory HLH protein Id2. Overexpres sion of Id2 in cortical progenitors completely inhibited the induction of n euron-specific genes and led to apoptosis, presumably as a consequence of c onflicting differentiation signals. Both of these phenotypes were rescued b y coexpression of a constitutively activated pRb mutant. In contrast, Id2 o verexpression in postmitotic cortical neurons affected neither neuronal gen e expression nor survival. Thus, pRb collaborates with HLHs to ensure the c oordinate induction of terminal mitosis and neuronal gene expression as cor tical progenitors become neurons.