RRC ID 57194
Author Read RD.
Title Pvr receptor tyrosine kinase signaling promotes post-embryonic morphogenesis, and survival of glia and neural progenitor cells in Drosophila.
Journal Development
Abstract Stem cells reside in specialized microenvironments, called niches, that regulate their development and the development of their progeny. However, the development and maintenance of niches are poorly understood. In the Drosophila brain, cortex glial cells provide a niche that promotes self-renewal and proliferation of neural stem cell-like cells (neuroblasts). In the central brain, neuroblasts and their progeny control post-embryonic morphogenesis of cortex glia through PDGF-like ligands, and this PDGFR receptor tyrosine kinase (RTK) signaling in cortex glia is required for expression of DE-cadherin, which sustains neuroblasts. Thus, through an RTK-dependent feed-forward loop, neuroblasts and their glial niche actively maintain each other. When the EGFR RTK is constitutively activated in cortex glia, they overexpress PDGF orthologs to stimulate autocrine PDGFR signaling, which uncouples their growth and survival from neuroblasts, and drives neoplastic glial transformation and elimination of neuroblasts. These results provide fundamental insights into glial development and niche regulation, and show that niche-neural stem cell feed-forward signaling becomes hijacked to drive neural tumorigenesis.
Volume 145(23)
Published 2018-12-4
DOI 10.1242/dev.164285
PII dev.164285
PMID 30327326
PMC PMC6288382
MeSH Animals Autocrine Communication Brain / growth & development Cell Proliferation Cell Survival Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / embryology* Drosophila melanogaster / enzymology Embryo, Nonmammalian / cytology* Embryo, Nonmammalian / enzymology Genetic Testing Morphogenesis* Neural Stem Cells / cytology* Neural Stem Cells / metabolism Neuroglia / cytology* Neuroglia / metabolism Neurons / cytology Neurons / metabolism Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction*
IF 5.763
Times Cited 3