Neuroblast niche position is controlled by PI3-kinase dependent DE-Cadherin adhesion

Abstract

Correct positioning of stem cells within their niche is essential for tissue morphogenesis and homeostasis. How stem cells acquire and maintain niche position remains largely unknown. Here, we show that a subset of brain neuroblasts (NBs) in Drosophila utilize Phosphoinositide 3-kinase (PI3-kinase) and DE-cadherin to build adhesive contact for NB niche positioning. NBs remain within their native microenvironment when levels of PI3-kinase activity and DEcadherin are elevated in NBs. This occurs through PI3-kinasedependent regulation of DE-Cadherin-mediated cell adhesion between NBs and neighboring cortex glia, and between NBs and their ganglion mother cell daughters. When levels of PI3-kinase activity and/or DE-Cadherin are reduced in NBs, NBs lose niche position and relocate to a non-native brain region that is rich in neurosecretory neurons, including those that secrete some of the Drosophila insulin-like peptides. Linking levels of PI3-kinase activity to the strength of adhesive attachment could provide cancer stem cells and hematopoietic stem cells with a means to cycle from trophicpoor to trophic-rich microenvironments.

Msps Governs Acentrosomal Microtubule Assembly and Reactivation of Quiescent Neural Stem Cells

“…Primary protrusion of qNSCs directly contacts with neuropil, however, proteins at NSC-neuropil contact sites were previously unknown. Cell adhesion molecule E-cad, abundantly expressed in 3 rd instar larval NSCs, is often localized to cell-cell contacts and was recently reported to localize to MB NSC-cortex glia contact in the adult Drosophila brain (Doyle et al, 2017;Dumstrei et al, 2003). We show, for the first time, that Ecad forms an endfeet-like structure at NSC-neuropil contact sites.…”

Pvr receptor tyrosine kinase signaling promotes post-embryonic morphogenesis, and survival of glia and neural progenitor cells in Drosophila

“…Previous studies show that extrinsic contact-dependent cues are required to polarize embryonic neuroblasts, which is essential for proper asymmetric cell division (Siegrist and Doe, 2006). DE-cadherin, a contact-dependent cue that is essential for neuroblast proliferation (Doyle et al, 2017;Dumstrei et al, 2003), showed reduced expression in cortex glia upon Pvr loss, and DE-cadherin co-overexpression largely rescued the effects of Pvr knockdown. In the Drosophila germline, DE-cadherin functions in homophilic adhesion between germline stem (GSCs) cells and niche cells, and this anchors GSCs to the niche to promote self-renewal and orient asymmetric cell division (Inaba et al, 2010;Song et al, 2002).…”

“…PI3K signaling is required in neuroblasts to maintain growth and proliferation throughout larval development (Chell and Brand, 2010;Cheng et al, 2011;Sousa-Nunes et al, 2011), and PI3K signaling in neuroblasts is required to anchor neuroblasts in the cortex glia niche through DE-cadherin-dependent adhesion (Doyle et al, 2017). DE-Cadherin is expressed in larval central brain cortex glia and localizes at the interface of cortex glia and central brain neuroblasts, and glial DE-cadherin (DEcad) function is essential for maintenance and proliferation of neuroblasts and their progeny (Dumstrei et al, 2003;Holcroft et al, 2013).…”

Eyeless uncouples mushroom body neuroblast proliferation from dietary amino acids in Drosophila

“…After thorough washing in 0.1% Triton-x/PBS, antibody staining was performed according to standard methods (Doyle et al, 2017; Siegrist et al, 2010). Primary antibodies used in this study were: chicken anti-GFP (1:100, Abcam, Cambridge, MA), rat anti-Deadpan (1:100, Abcam), rabbit anti-Scribble (1:200; gift of C. Doe), and rabbit anti-Eyeless (1:1000; gift of U. Waldorf).…”