ANALYZING THE FUNCTIONS OF PREFOLDIN COMPLEX IN NEUROBLAST HOMEOSTASIS OF DROSOPHILA MELANOGASTER

Abstract

Prefoldin is a molecular chaperone that regulates tubulin function in mitosis. In this thesis, I show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with dramatic neuroblast overgrowth, due to the severe asymmetric division defects of both neuroblasts and Intermediate Neural Progenitors (INPs). Co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α- or β-tubulin in pins- mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins mutant brains. These data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells.