Laminin β2 Chain Regulates Retinal Progenitor Cell Mitotic Spindle Orientation via Dystroglycan

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Dmitri SerjanovWilliam J Brunken

Abstract

Vertebrate retinal development follows a pattern during which retinal progenitor cells (RPCs) give rise to all retinal cell types in a highly conserved temporal sequence. RPC proliferation and cell cycle exit are tightly coordinated to ensure proper and timely production of each of the retinal cell types. Extracellular matrix (ECM) plays an important role in eye development, influencing RPC proliferation and differentiation. In this study, we demonstrate that laminins, key ECM components, in the inner limiting membrane, control mitotic spindle orientation by providing environmental cues to the RPCs. In vivo deletion of laminin β2 in mice of both sexes results in a loss RPC basal processes and contact with the ECM, leading to a shift of the mitotic spindle pole orientation toward asymmetric cell divisions. This leads to decreased proliferation and premature RPC pool depletion, resulting in overproduction of rod photoreceptors at the expense of bipolar cells and Müller glia. Moreover, we show that deletion of laminin β2 leads to disruption and mislocalization of its receptors: dystroglycan and β1-integrin. Addition of exogenous β2-containing laminins to laminin β2-deficient retinal explants stabilizes the RPC basal processes and ...Continue Reading

Citations

Sep 15, 2020·Frontiers in Molecular Neuroscience·Michihiro IgarashiMotohiro Nozumi
Dec 5, 2019·Genes·Peter M J Quinn, Jan Wijnholds

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