“Neurodevelopment in a dish” Elucidates the Mechanisms of Autism Spectrum Disorder

Abstract

Introduction

Autism spectrum disorders (ASD) is a group of neurodevelopmental disorders characterized by deficits in social cognition, communication, and behavioral flexibility. Most of the cases appear to be caused by the combination of autism risk genes and environmental factors affecting early embryonal brain development. The current animal and 2D cellular models are not able to recapitulate the complex integrity of the developing brain. Therefore a model of the brain that can cast a light on the pathological processes during brain development is of a high need.

Aim and objectives

The aim of our research is to develop a three-dimensional brain organotypic system (brain organoids) for culturing patient's derived induced pluripotent stem cells (iPSC).

Methodology

We propose a multidisciplinary approach, involving the generation of patient specific iPSC from somatic cells (fibroblasts) and 3D culturing techniques to build a complex “humanized” in vitro platform for ASD research. Further we will investigate differences in gene expression of potential disease related markers and cellular phenotype between autistic patients and controls.

Results

Brain organoids have the ability to recreate the right complexity of the brain. On the cellular and gene expression level, organoids demonstrate a high similarity to the neurodevelopment in vivo and can therefore recapitulate early stages of the neurogenesis.

Conclusion

To date organoids are the most relevant cellular in vitro platform for the understanding the mechanisms behind ADS pathology. Organoids are a good modeling system for elucidating the role of epigenetic and environmental factors for development of ASD.

Disclosure of interest

The authors have not supplied their declaration of competing interest.