Asymmetric cell division in the regulation of neural stem cell self-renewel in Drosophila Melanogaster

Abstract

Stem cells are capable of self-renewal and differentiation. Drosophila larval brain neural stem cells, neuroblasts, divide asymmetrically to self-renew and to produce differentiated daughters. Defects in asymmetric division can result in excess neuroblast self-renewal and/or aberrant differentiation. More importantly, it can lead to hyperproliferation, a phenotype resembling brain tumors. During asymmetric division of neuroblasts, several proteins controlling the self-renewal versus differentiation decision, including proliferation factor atypical protein kinase (aPKC) and the differentiation factor Numb, are asymmetrically localized and preferentially segregated into one daughter cell. This thesis describes two novel players in the asymmetric division and self-renewal of Drosophila neuroblasts that inhibit excess neuroblast self-renewal through distinct pathways. The first is a novel zinc-finger protein, Zif, which regulates the expression and asymmetric localization of aPKC to prevent excess neuroblast self-renewal. The second is the Drosophila Protein Phosphatase 2A (PP2A), a brain tumor suppressor that inhibits excess self-renewal by regulating asymmetric localization/activation of Numb through the promotion of Polo expression.