RRC ID 76041
Author Rawsthorne H, Calahorro F, Holden-Dye L, O' Connor V, Dillon J.
Title Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour.
Journal PLoS One
Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organism C. elegans provides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulate C. elegans food leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identify C. elegans orthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism in C. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.
Volume 16(5)
Pages e0243121
Published 2021-1-1
DOI 10.1371/journal.pone.0243121
PII PONE-D-20-37216
PMID 34043629
PMC PMC8158995
MeSH Animals Autism Spectrum Disorder / genetics* Autism Spectrum Disorder / physiopathology Behavior, Animal* Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Disease Models, Animal Epigenomics Humans Mutation / genetics Social Behavior*
C.elegans tm669 tm3785 tm1961 tm625 tm748 tm1738 tm3536 tm3645