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Engrailed2 and Cerebellar Development in the Pathogenesis of Autism Spectrum Disorders

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Autism

Part of the book series: Current Clinical Neurology ((CCNEU))

Abstract

Autism and autism spectrum disorders (ASD) are complex neurodevelopmental diseases with strong genetic etiologies. While many brain regions are implicated in ASD pathogenesis, many studies demonstrate that the cerebellum is consistently abnormal in ASD patients, both neuroanatomically and functionally. Recently, the human gene ENGRAILED2 (EN2), an important regulator of cerebellar development, was identified as an ASD-susceptibility gene, a finding replicated in three data sets. We review much of the literature implicating an abnormal cerebellum in ASD, as well as the molecular and cellular development of the cerebellum with respect to possible pathogenetic mechanisms that contribute to the ASD phenotype. In addition, we explore the role of EN2 in normal cerebellar development as well as animal models in which abnormal En2 expression produces ASD-like behavior and neuropathology. We also share preliminary data from our laboratory that suggest that En2 promotes postnatal cerebellar development via cell cycle regulation and interactions with extracellular growth signals. After reviewing these data from different disciplines, it is our hope that the reader will better understand how abnormal cerebellar development contributes to ASD pathophysiology and pathogenesis. Further, we underscore the importance of multidisciplinary approaches to identifying ASD-associated genes and their functions during development of brain structures known to be abnormal in ASD patients.

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Rossman, I.T., DiCicco-Bloom, E. (2008). Engrailed2 and Cerebellar Development in the Pathogenesis of Autism Spectrum Disorders. In: Autism. Current Clinical Neurology. Humana Press. https://doi.org/10.1007/978-1-60327-489-0_1

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