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Genetic control of cellular morphogenesis in Muller glia.

ABSTRACT: Cell shape is critical for the proper function of every cell in every tissue in the body. This is especially true for the highly morphologically diverse neural and glia cells of the central nervous system. The molecular processes by which these, or indeed any, cells gain their particular cell-specific morphology remain largely unexplored. To identify the genes involved in the morphogenesis of the principal glial cell type in the vertebrate retina, the Müller glia (MG), we used genomic and CRISPR based strategies in zebrafish (Danio rerio). We identified 41 genes involved in various aspects of MG cell morphogenesis and revealed a striking concordance between the sequential steps of anatomical feature addition and the expression of cohorts of functionally related genes that regulate these steps. We noted that the many of the genes preferentially expressed in zebrafish MG showed conservation in glia across species suggesting evolutionarily conserved glial developmental pathways.

SUBMITTER: Charlton-Perkins M

PROVIDER: S-EPMC6563441 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genetic control of cellular morphogenesis in Müller glia.

Charlton-Perkins Mark M Almeida Alexandra D AD MacDonald Ryan B RB Harris William A WA

Glia 20190329 7

Cell shape is critical for the proper function of every cell in every tissue in the body. This is especially true for the highly morphologically diverse neural and glia cells of the central nervous system. The molecular processes by which these, or indeed any, cells gain their particular cell-specific morphology remain largely unexplored. To identify the genes involved in the morphogenesis of the principal glial cell type in the vertebrate retina, the Müller glia (MG), we used genomic and CRISPR ...[more]

PMID: 30924555

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Genetic control of cellular morphogenesis in Müller glia

Project description:How the various cell-types of the body achieve their specific shapes is fundamentally unknown. Here, we explore this issue by identifying genes involved in the elaboration of the complex, yet conserved, cellular morphology of Müller glial (MG) cells in the retina. Using genomic based strategies in zebrafish, we found more than 40 candidate genes involved in specific aspects of MG morphogenesis. The successive steps of cell morphogenesis correlate with the timing of the expression of cohorts of inter-related genes that have roles in generating the particular anatomical features of these cells, suggesting that a sequence of genetic regulomes govern stepwise cellular morphogenesis in this system.

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Genetic control of cellular morphogenesis in Müller glia

Project description:Genetic control of cellular morphogenesis in Müller glia

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Project description:Over- and underexposure to cholesterol activates glia in neurodegenerative brain and retinal diseases but the molecular targets of cholesterol in glial cells are not known. Here, we report that disruption of unesterified membrane cholesterol content modulates the transduction of chemical, mechanical and temperature stimuli in mouse Müller cells. Activation of TRPV4 (transient receptor potential vanilloid type 4), a nonselective polymodal cation channel was studied following the removal or supplementation of cholesterol using the methyl-beta cyclodextrin (MβCD) delivery vehicle. Cholesterol extraction disrupted lipid rafts and caveolae without affecting TRPV4 trafficking or membrane localization protein. However, MβCD suppressed agonist (GSK1016790A)- and temperature-evoked elevations in [Ca2+ ]i , and suppressed transcellular propagation of Ca2+ waves. Lowering the free membrane cholesterol content markedly prolonged the time-course of the glial swelling response, whereas MβCD:cholesterol supplementation enhanced agonist- and temperature-induced Ca2+ signals and shortened the swelling response. Taken together, these data show that membrane cholesterol modulates polymodal transduction of agonists, swelling and temperature stimuli in retinal radial glia and suggest that dyslipidemic retinas might be associated with abnormal glial transduction of ambient sensory inputs.

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