Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system

Functional analyses of neural RNA-binding proteins have focused mainly on t heir roles as modulators of posttranscriptional gene regulation, e.g., alte rnative splicing, dendritic mRNA localization, and local translation. Here we identified a mouse homologue of human IMP3, which is known to bind to an d repress the translation of igf2 leader 3 mRNA. The mouse igf2 mRNA-bindin g protein 3 (mIMP3) is a member of the zipcode binding protein-1 (ZBP-1) fa mily previously reported in chick fibroblast cells, mIMP3 was expressed in undifferentiated neuroepithelial cells and some postmitotic neurons at earl y embryonic stages (E10.5-E12.5), and its expression level decreased after the midembryonic stage (E12.5) until birth. The expression profile of mIMP3 is very similar to that of mouse igf2 leader 3 mRNA. In vitro UV crosslink ing experiments showed that mIMP3 preferentially bound to igf2 leader 3 mRN A rather than igf2 leader 4 mRNA and did not bind the zipcode region of p-a ctin or c-myc mRNA, Furthermore, persistent expression of mIMP3 protein in an undifferentiated P19 cell line revealed that mIMP3 inhibited neuronal di fferentiation morphologically and immunohistochemically. Taken together, th ese observations raise the possibility that mIMP3 represses neuronal differ entiation through the regulation of igf2 mRNA expression. J, Neurosci, Res. 64, 132-143, 2001. (C) 2001 Wiley-Liss, Inc.