RT Journal Article
SR Electronic
T1 Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 121756
DO 10.1101/121756
A1 Reena Clements
A1 Rolf Turk
A1 Kevin P. Campbell
A1 Kevin M. Wright
YR 2017
UL http://biorxiv.org/content/early/2017/03/29/121756.abstract
AB 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 precise role for dystroglycan in regulating retinal development remains poorly understood. Using a mouse model of dystroglycanopathy (ISPDL79*) and conditional dystroglycan mutants, 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.