Regulation of Ribosomal Biogenesis in Neural Precursors by Bhlh Proneural Proteins

Highly conserved bHLH proneural proteins Achaete (Ac) and Scute (Sc) and their mammalian homologue ASCL1 specify neural precursors and initiate neuronal reprogramming from the non-neural tissue. Previous studies have shown that proneural proteins specify neural fate by transcriptional activation of an array of downstream target genes. Strikingly, we discovered that Ac localizes to nucleolus during precursor specification, and this processes is mediated by the highly conserved actin-related protein 6 (Arp6). In Arp6 mutants, proneural proteins are excluded from nucleolus, and precursor specification is delayed, leading to smaller external sensory (ES) organs. Smaller ES organ was also observed in mutants lacking ribosomal subunits or nucleolar proteins, suggesting that Arp6-meidated nucleolar localization of proneural proteins regulates ribosome biogenesis in neural precursors. In this proposal, therefore, we would like to explore the regulation of ribosome biogenesis by proneural proteins and Arp6 in neural precursor specification. We will study the conservation and specificity of the nucleolar localization of different fly and mammalian proneural proteins. We will also investigate the functions of Ac/Arp6 complex to regulate translational efficiency of neural precursor proteins and ribosome subunit assembly in culture cells and in fly. These analyses will not only reveal novel insights for proneural protein-mediated neurogenesis in animals, but might also suggest new mechanism for proneural protein-mediated neuronal reprogramming.

Project ID:PA10708-1014
External Project ID:MOST107-2311-B182-005