Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism

Increased brain size is common in children with autism spectrum disorders. Here we propose that an increased number of cortical excitatory neurons may underlie the increased brain volume, minicolumn pathology and excessive network excitability, leading to sensory hyper-reactivity and seizures, which are often found in autism. We suggest that Fibroblast Growth Factors (FGF), a family of genes that regulate cortical size and connectivity, may be responsible for these developmental alterations. Studies in animal models suggest that mutations in FGF genes lead to altered cortical volume, excitatory cortical neuron number, minicolum pathology, hyperactivity and social deficits. Thus, many risk factors may converge upon FGF-regulated pathogenetic pathways, which alter excitatory/inhibitory balance and cortical modular architecture, and predispose to autism spectrum disorders.