Abstract
Postmortem neuropathological studies of autism consistently reveal distinctive types of malformations, including cortical dysplasias, heterotopias, and various neuronomorphometric abnormalities. In keeping with these observations, we review here that 88% of high-risk genes for autism influence neural induction and early maturation of the neuroblast. In addition, 80% of these same genes influence later stages of differentiation, including neurite and synapse development, suggesting that these gene products exhibit long-lasting developmental effects on cell development as well as elements of redundancy in processes of neural proliferation, growth, and maturation. We also address the putative genetic overlap of autism with conditions like epilepsy and schizophrenia, with implications to shared and divergent etiologies. This review imports the necessity of a frameshift in our understanding of the neurodevelopmental basis of autism to include all stages of neuronal maturation, ranging from neural induction to synaptogenesis.
Highlights
Neuroblasts require precise extrinsic and intrinsic signals to acquire their unique, semi-predetermined identities
Though signals for growth and differentiation may funnel through similar pathways for all neurons, such as the Wingless Integration Site (Wnt), Hedgehog, and Transforming Growth Factor-β (TGF-β) families, the effectors that regulate these pathways can vary considerably from one brain structure to the allowing the creation of distinct boundaries and the refinement of cellular identities (Wolpert and Kerszberg, 2003)
In addition to reviewing the various functions of each gene product, we studied their involvements in epilepsy and schizophrenia
Summary
Neuroblasts require precise extrinsic and intrinsic signals to acquire their unique, semi-predetermined identities. Other genes may express considerable functional redundancy at numerous stages of cell growth and development, likewise leading to shared disturbances in neurogenesis and neurite extension or synaptogenesis.
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