The research proposal is designed to elucidate the molecular mechanisms regulating developmental programs. A particular type of transcriptional regulators, the basic helix-loop-helix (bHLH) proteins, have been implicated in cell proliferation and differentiation in several systems. The dominant negative (dn) HLH proteins (ld1, ld2, ld3, ld4 and emc) appear to act as general antagonists of differentiation by inhibiting bHLH proteins. The dnHLH protein ld2 is also involved in cell cycle regulation since interaction of ld2 with the retinoblastoma Earotein (pRb) resulls in cell cycle progression. Targeted disruption of the dnHLH genes ld4 and ld2 will be performed to analyse the in vivo function of the gene products. Expression of dnHLH genes in neural precursors strongly suggests, that gene disruption of ld2 and ld4 effects the neural embryogenic development. Detailed analysis of the null mutants will reveal new molecular aspects of differentiation and proliferalioll processes dul ing neurogenesis.