The extracellular matrix provides directional cues for neuronal migration during cerebellar development

Abstract

Normal central nervous system development relies on accurate intrinsic cellular programs as well as on extrinsic informative cues provided by extracellular molecules. Migration of neuronal progenitors from defined proliferative zones to their final location is a key event during embryonic and postnatal development. Extracellular matrix components play important roles in these processes, and interactions between neurons and extracellular matrix are fundamental for the normal development of the central nervous system. Guidance cues are provided by extracellular factors that orient neuronal migration. During cerebellar development, the extracellular matrix molecules laminin and fibronectin give support to neuronal precursor migration, while other molecules such as reelin, tenascin, and netrin orient their migration. Reelin and tenascin are extracellular matrix components that attract or repel neuronal precursors and axons during development through interaction with membrane receptors, and netrin associates with laminin and heparan sulfate proteoglycans, and binds to the extracellular matrix receptor integrins present on the neuronal surface. Altogether, the dynamic changes in the composition and distribution of extracellular matrix components provide external cues that direct neurons leaving their birthplaces to reach their correct final location. Understanding the molecular mechanisms that orient neurons to reach precisely their final location during development is fundamental to understand how neuronal misplacement leads to neurological diseases and eventually to find ways to treat them.

Micropatterned ECM substrates reveal complementary contribution of low and high affinity ligands to neurite outgrowth

“…In this study, we used a novel molecular microcontact printing (lCP) device [Nettikadan et al, 2006] to deposit laminin (LN) and fibronectin (FN), two major ECM components. Both play a crucial role during nervous system development in promoting cell adhesion, and regulating neurite outgrowth and guidance during neurite development and, as studied here, axonal regeneration of adult neurons [Westerfield, 1987;Powell and Kleinman, 1997;Porcionatto, 2006]. Our results show that neurite morphology, growth dynamics, and cytoskeletal reorganization are largely stimulated by binding of LN ligand, in contrast to FN.…”

Extracellular Matrix: Functions in the Nervous System

“…Many neurons use basal RGC processes as a scaffold for migration. The ECM shapes the niche where NSCs reside, modulates their maintenance and differentiation, and influences migration of their progeny (Sobeih and Corfas 2002;Porcionatto 2006;von Holst 2008).…”

Cerebellar Migration Defects in Aicardi Syndrome: An Extension of the Neuropathological Spectrum

“…This tangential migration is due to the combined action of chemorepellent and chemoattractant cues, leading to the formation of the external germinal layer [55][56][57]. Radial migration is observed during postnatal cerebellar development, when granule cell precursors migrate out of the external granule cell layer, perpendicular to the surface, using Bergmann glial fibers as support [55].…”

“…Guidance cues provided by soluble factors and by extracellular matrix components play a fundamental role in the oriented migration of neuronal progenitors [55]. Laminin, fibronectin, and vitronectin are extracellular matrix molecules that support neuronal migration; chondroitin sulfate proteoglycans molecules function as barriers for migration; and reelin, netrins, and tenascins molecules orient the migrating neurons to reach their correct locations [55].…”

“…Laminin, fibronectin, and vitronectin are extracellular matrix molecules that support neuronal migration; chondroitin sulfate proteoglycans molecules function as barriers for migration; and reelin, netrins, and tenascins molecules orient the migrating neurons to reach their correct locations [55]. When a fraction of newly postmitotic neurons become incapable of leaving the ventricular zone, they remain as clumps or nodules along the ventricular zone, resulting in periventricular heterotopia [50].…”