MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development

Cell Death Dis. 2018 Sep 24;9(10):999. doi: 10.1038/s41419-018-1027-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cerebellar Cortex / growth & development*
  • Cerebellar Cortex / metabolism
  • Cognitive Dysfunction / metabolism*
  • Exercise Test
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Knockout Techniques
  • Integrin beta1 / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Movement / physiology*
  • Neurogenesis / physiology
  • Neuroglia / metabolism*
  • Neurons / metabolism*
  • Phosphorylation
  • Purkinje Cells / metabolism

Substances

  • Integrin beta1
  • MARVELD1 protein, mouse
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse