Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0026850 (
muscular dystrophy
)
5,870
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 of 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. 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.
...
PMID:Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development. 2876 Aug 65
