Logo image
Back
Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development
Preprint   Open access

Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development

Reena Clements, Rolf Turk, Kevin P Campbell and Kevin M Wright
bioRxiv: the preprint server for biology
Cold Spring Harbor Laboratory
03/29/2017
DOI: 10.1101/121756
url
https://doi.org/10.1101/121756View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Proper neural circuit formation requires the precise regulation of neuronal migration, axon guidance and dendritic arborization. Mutations affecting the function of the transmembrane glycoprotein dystroglycan cause a form of congenital muscular dystrophy that is frequently associated with neurodevelopmental abnormalities. Despite its importance in brain development, the role for dystroglycan in regulating retinal development remains poorly understood. Using a mouse model of dystroglycanopathy ( ISPD L79* ) and conditional dystroglycan mutants of both sexes, we show that dystroglycan is critical for the proper migration, axon guidance and dendritic stratification of neurons in the inner retina. Using genetic approaches, we show that dystroglycan functions in neuroepithelial cells as an extracellular scaffold to maintain the integrity of the retinal inner limiting membrane (ILM). Surprisingly, despite the profound disruptions in inner retinal circuit formation, spontaneous retinal activity is preserved. These results highlight the importance of dystroglycan in coordinating multiple aspects of retinal development. Significance Statement The extracellular environment plays a critical role in coordinating neuronal migration and neurite outgrowth during neural circuit development. The transmembrane glycoprotein dystroglycan functions as a receptor for multiple extracellular matrix proteins, and its dysfunction leads to a form of muscular dystrophy frequently associated with neurodevelopmental defects. Our results demonstrate that dystroglycan is required for maintaining the structural integrity of the inner limiting membrane (ILM) in the developing retina. In the absence of functional dystroglycan, ILM degeneration leads to defective migration, axon guidance and mosaic spacing of neurons, and a loss of multiple neuron types during retinal development. These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy.

Details

Metrics

10 Record Views
Logo image