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Laminin γ3 plays an important role in retinal lamination, photoreceptor organisation and ganglion cell differentiation

Lookup NU author(s): Majed Felemban, Alex Sharpe, Dr Roman Bauer, Dr Dean Hallam, David Steel, Professor Susan Lindsay, Dr Carla Mellough, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Laminins are heterotrimeric glycoproteins of the extracellular matrix. 11 different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin α1, α5, β1, β2 and γ1 to be predominantly expressed in Bruch’s membrane and inner limiting membrane. Laminin-332 and laminin γ3 expression were predominant in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin γ3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organization and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin γ3 during human retinogenesis.


Publication metadata

Author(s): Dorgau B, Felemban N, Sharpe A, Bauer R, Hallam D, Steel DH, Lindsay S, Mellough C, Lako M

Publication type: Article

Publication status: Published

Journal: Cell Death and Disease

Year: 2018

Volume: 9

Issue: 6

Print publication date: 01/06/2018

Online publication date: 23/05/2018

Acceptance date: 26/04/2018

ISSN (print): 2041-4889

ISSN (electronic): 2041-4889

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41419-018-0648-0

DOI: 10.1038/s41419-018-0648-0


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