ANALYSIS OF TWO NOVEL COMPLEXES THAT REGULATE NEUROBLAST SELF-RENEWAL AND ASYMMETRIC DIVISION IN DROSOPHILA MELANOGASTER
Drosophila neuroblast divides asymmetrically to produce a self-renewing neuroblast and a ganglion mother cell that is committed to differentiation. The balance between neuroblast self-renewal and differentiation is tightly controlled to ensure the proper development of the central nervous system. In this thesis, I will describe two novel players that regulate Drosophila neuroblast asymmetric cell division. The first one is a multi-protein ubiquitin ligase, SCF-Slimb that is composed of SkpA, Cullin1, Roc1a and Slimb. The SCF-Slimb complex inhibits neuroblast self-renewal by regulating the polarized localization of atypical protein kinase C (aPKC) and cell fate determinant Numb, as well as mitotic spindle orientation in neuroblasts. The other player is Drosophila cytoplasmic dynein light chain 1, also named Cut up (Ctp). Ctp localizes at centrioles and controls the mitotic spindle orientation in neuroblasts. Ctp directly interacts with a centriolar protein Anastral Spindle 2 (Ana2) and regulates the localization of Mushroom body defect (Mud). Ana2, Ctp and Mud form a protein complex to regulate spindle orientation in neuroblasts.
neuroblast; self-renewal; asymmetric division; cut up; SCF; Drosophila
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