Postnatal Migration of Cerebellar Interneurons.

Ludovic Galas,Damien Schapman,Yutaro Komuro,Alexis Lebon,Hubert Vaudry,David Vaudry,Magalie Bénard,Hitoshi Komuro

doi:10.3390/brainsci7060062

Abstract

Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders.

Highlights

Over the last 100 years, the cerebellum has served as a model system to elucidate the cellular and molecular mechanisms underlying the development of the entire brain
There is a wide variety of cerebellum-linked disorders including autism spectrum disorders, neuropsychiatric illnesses, encephalopathy, hypoplasia, cerebellar ataxia, foetal Minamata disease (FMD), foetal alcohol spectrum disorders” (FASDs), foetal alcohol syndrome” (FAS), stuttering, diabetes or medulloblastoma [80,112,113] and emerging strategies with human induced pluropotent stem cells are proposed for regenerative neurology [114]
How the cerebellum grows and develops, when cell populations have particular vulnerabilities, and how we identify the complications of pathological development, are crucial questions and fascinating research avenues

Summary

Introduction

Over the last 100 years, the cerebellum has served as a model system to elucidate the cellular and molecular mechanisms underlying the development of the entire brain. Brain Sci. 2017, 7, 62 regarding the cellular mechanisms underlying neuronal migration was made from a study examining the migration of cerebellar granule cells. Among the studies, using cultured cerebellar neurons and an in vitro assay system for cell movement, Edmondson and Hatten revealed for the first time a critical role of cell adhesion molecules (astrotactin) in the glia-associated migration of immature neurons [4]. It has been subsequently demonstrated that the cellular and molecular mechanisms underlying the control of neuronal migration in the developing cerebellum can be generalized to the migration of many neurons in other brain regions, including the developing cerebrum, with few differences. The gathered knowledge illustrating the precise mechanisms of cerebellar development will in turn contribute to the development of therapeutic strategies aimed at curing brain disorders

Postnatal Cerebellum

Findings

Conclusions