Drosophila neuroblasts as a new model for the study of stem cell self-renewal and tumour formation

Abstract

Drosophila larval brain stem cells (neuroblasts) have emerged as an important model for the study of stem cell asymmetric division and the mechanisms underlying the transformation of neural stem cells into tumour-forming cancer stem cells. Each Drosophila neuroblast divides asymmetrically to produce a larger daughter cell that retains neuroblast identity, and a smaller daughter cell that is committed to undergo differentiation. Neuroblast self-renewal and differentiation are tightly controlled by a set of intrinsic factors that regulate ACD (asymmetric cell division). Any disruption of these two processes may deleteriously affect the delicate balance between neuroblast self-renewal and progenitor cell fate specification and differentiation, causing neuroblast overgrowth and ultimately lead to tumour formation in the fly. In this review, we discuss the mechanisms underlying Drosophila neural stem cell self-renewal and differentiation. Furthermore, we highlight emerging evidence in support of the notion that defects in ACD in mammalian systems, which may play significant roles in the series of pathogenic events leading to the development of brain cancers.

Drosophila Embryonic CNS Development: Neurogenesis, Gliogenesis, Cell Fate, and Differentiation

“…Apical par complex formation and function: One key role of the apically localized Par complex is to direct the localization of the basal proteins, Miranda (Mira) and Partner of Numb (Pon), to the basal cortex (Li et al 2014b;Gallaud et al 2017). The functional Par complex consists of Par-6, atypical Protein Kinase C (aPKC), and Bazooka (Baz).…”

Arl2- and Msps-dependent microtubule growth governs asymmetric division

“…Self-renewal and differentiation are two key features of stem cells. In Drosophila melanogaster, larval brain neural stem cells, or neuroblasts (NBs), divide asymmetrically to give rise to a self-renewing NB and a ganglion mother cell (GMC) that generates two post-mitotic neurons ( Doe, 2008 ; Wu et al, 2008 ; Knoblich, 2010 ; Gonzalez, 2013 ; Jiang and Reichert, 2014 ; Li et al, 2014 ). During each asymmetric division, cell polarity is established by apically localized Par proteins, including atypical PKC (aPKC), Bazooka (the Drosophila homologue of Par3), and Par6 ( Wodarz et al, 1999 , 2000 ; Petronczki and Knoblich, 2001 ).…”

Knockdown of CRAD suppresses the growth and promotes the apoptosis of human lung cancer cells via Claudin 4

“…Self-renew or colony formation is a feature of cancer cells [ 24 , 25 ]. We next investigated the effects of CRAD knockdown on the colony formation of lung cancer cells.…”