Above genetics: Lessons from cerebral development in autism

Abstract

While a distinct minicolumnar phenotype seems to be an underlying factor in a significant portion of cases of autism, great attention is being paid not only to genetics but to epigenetic factors which may lead to development of the conditions. Here we discuss the indivisible role the molecular environment plays in cellular function, particularly the pivotal position which the transcription factor and adhesion molecule, β-catenin, occupies in cellular growth. In addition, the learning environment is not only integral to postnatal plasticity, but the prenatal environment plays a vital role during corticogenesis, neuritogenesis, and synaptogenesis as well. To illustrate these points in the case of autism, we review important findings in genetics studies (e.g., PTEN, TSC1/2, FMRP, MeCP2, Neurexin-Neuroligin) and known epigenetic factors (e.g., valproic acid, estrogen, immune system, ultrasound) which may predispose towards the minicolumnar and connectivity patterns seen in the conditions, showing how one-gene mutational syndromes and exposure to certain CNS teratogens may ultimately lead to comparable phenotypes. This in turn may shed greater light on how environment and complex genetics combinatorially give rise to a heterogenetic group of conditions such as autism.

Autism as a sequence: From heterochronic germinal cell divisions to abnormalities of cell migration and cortical dysplasias

“…Prenatal ultrasound was deregulated in the early 1990’s and an eightfold increase in energy was allowed by the FDA in order to better visualize the fetus. This increase closely parallels the rise in prevalence observed for autism spectrum disorders (78, 79). It is well known that high frequency sound waves affect various stem cell populations and are capable of regulating a number of growth factors (78, 79).…”

“…This increase closely parallels the rise in prevalence observed for autism spectrum disorders (78, 79). It is well known that high frequency sound waves affect various stem cell populations and are capable of regulating a number of growth factors (78, 79). Ultrasound is known to trigger tissue regeneration in bone fractures and has similar effects on cartilage.…”

Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism Pathogenesis?

“…Although it is still far from clear, it is becoming widely accepted that neurodevelopmental disorders, including autism, display defects in neuronal organization and plasticity. Abnormalities of brain growth and connectivity in autism are usually apparent after the first year of life (Courchesne et al 2003;Williams and Casanova 2011), a period characterized by intensive remodellation of neuronal tissue. The organization, development and function of complex brain networks depend on numerous neuronal precursors differentiating to specific neuron or glial cell populations.…”

Association Analysis of Two Single-Nucleotide Polymorphisms of theRELNGene with Autism in the South African Population

“…Based on the evidence reviewed by Elsabbagh et al (2012), the median of worldwide prevalence estimates of ASDs is 62/10,000. A number of studies have given substantial evidence that points toward the role of genetic (Folstein and Rosen-Sheidley, 2001;Williams and Casanova, 2011;Neale et al, 2012) and environmental factors (Rodier, 2000;Acosta and Pearl, 2003) in the etiology of autism, which further show autism as a multifactorial trait. It has already been clear from various twin studies that the risk of autism is higher among siblings of affected individuals.…”