Abstract
The establishment of functional neuronal connectivity is dependent on the neuronal migration and the accurate positioning of neurons in the developing brain. Abnormal neuronal migration can trigger neuronal maturation defects and apoptosis. However, many genetic bases remain unclear in neuronal migration disorders during brain development. In this study, we reported that MARVELD1-defected mice displayed motor and cognitive dysfunction resulting from aberrant neuronal migration during brain development. The laminar organization of the cerebral cortex and cerebellum in MARVELD1 knockout (KO) mice is disrupted, indicating impaired radial neuronal migration. Furthermore, we used the cerebellum as a model to explore the radial neuronal migration processes, and the results demonstrated that the proper neuronal migration depended on MARVELD1 expression in glial cells of the developing brain. MARVELD1 suppressed the expression of ITGB1 and FAK Tyr397 phosphorylation in glia-dependent manner. The inhibition of the MARVELD1/ITGB1/FAK signalling pathway in MARVELD1 KO mice could reverse the defects in neuronal migration in vitro. Our findings revealed that MARVELD1 regulated neuronal migration by mediating the formation of glial fibres and ITGB1/FAK signalling pathway. The depletion of MARVELD1 during mouse brain development led to the abnormity of motor and cognition functions.
Highlights
The emergence of mature neurons and the functional neuronal connectivity depends on neuronal migration in the developing brain[1,2,3]
Based on the consideration that the cerebellum is a good model to study the origin of migration deficits[4,29,30], we focused on the cerebellum to explore the migrating process
Recent studies in C. elegans had identified several developmental regulatory patterns that persisted into ageing and effectively limited the lifespan[47,48]
Summary
The emergence of mature neurons and the functional neuronal connectivity depends on neuronal migration in the developing brain[1,2,3]. Newborn projection neurons in the cerebral cortex and granule cells in the cerebellum arrived at their target locations via this migrating pattern[1,2,6,7]. It is found that membrane-related signal events play crucial roles in the control of neuronal radial migration[5,8,9]. Some transduction paradigms of these signal molecules, such as interactions of cell adhesion molecules, have been illustrated as critical mechanisms underlying radial migration[1,8,9]. It is reported that ITGB11,10,11, Astn 1/21,12, N-cadherin[5,13] and connexins[1,14] can ensure the adhesion of the neuron to glial fibres during the process of neuronal radial migration
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