Activation of helix-loop-helix proteins Id1, Id2 and Id3 during neural differentiation

Id is a nuclear factor containing a helix-loop-helix (HLH) motif. It has been reported that Id functions as an inhibitor of cell differentiation and its gene expression is down-regulated during cell differentiation. We have characterized three Id-related cDNAs, Id1, Id2 and Id3, isolated from nerve growth factor (NGF)-stimulated PC12 cells. Structural analysis revealed that all three Id's contain putative phosphorylation sites for cyclic AMP-dependent kinase, casein kinase II and protein kinase C near and inside the HLH motifs. In contradiction to the previous reports, Northern blot analysis revealed that NGF induces rapid and transient increase of all three Id gene transcriptions. Furthermore, in situ hybridization of rat embryo showed that all three Id genes are highly expressed in neural precursors rather than differentiated neural cells. These results indicate that Id family members may function as immediate-early gene products, and that the expression of the Id family may play an important role in the early stage of neural differentiation.