title: Neuroblast niche position is controlled by Phosphoinositide 3-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) inDrosophilautilize 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 DE-cadherin are elevated in NBs. This occurs through PI3-kinase-dependent 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 theDrosophilainsulin-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 trophic-poor to trophic-rich microenvironments.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Doyle
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pahl
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Karsten H
authors.initials: KH
authors.lastname: Siller
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Ardiff
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22903, USA ses4gr@virginia.edu.
authors.forename: Sarah E
authors.identifier: 0000-0003-0685-5387
authors.initials: SE
authors.lastname: Siegrist
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000254:growth & development; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008938:Mitosis; D009024:Morphogenesis; D058953:Neural Stem Cells / Q000166:cytology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases
keywords: DE-Cadherin; Drosophila; Neuroblast; Niche; PI3-kinase; Shotgun; Stem cell