Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions i
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REVIEW
Open Access
Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology Cristina Cheroni1,2*†, Nicolò Caporale1,2,3*† and Giuseppe Testa1,2,3*
Abstract The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals’ genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment. Keywords: Autism spectrum disorder, Neurodevelopmental disorders, Pluripotent stem cells, Brain organoids, Developmental neurotoxicology, Endocrine disruptors, Gene × environment
* Correspondence: [email protected]; [email protected]; [email protected]; [email protected]; [email protected] † Cristina Cheroni and Nicolò Caporale contributed equally to this work. 1 High Definition Disease Modelling Lab, Stem Cell and Organoid Epigenetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the
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