Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism associated gene
Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism associated gene
Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism, there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, Caenorhabditis elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms, it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilize this social behaviour to investigate the effect of autism-associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight into complex social behaviour.
3546-3553
Rawsthorne-Manning, Helena
17228f7b-6d7b-4f73-9dbc-6849c3f1f496
Calahorro Nunez, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Feist, Emily
17090654-ab15-4e64-aaa1-2e0f199365e7
Holden-Dye, Linda
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O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Rawsthorne-Manning, Helena
17228f7b-6d7b-4f73-9dbc-6849c3f1f496
Calahorro Nunez, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Feist, Emily
17090654-ab15-4e64-aaa1-2e0f199365e7
Holden-Dye, Linda
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Rawsthorne-Manning, Helena, Calahorro Nunez, Fernando, Feist, Emily, Holden-Dye, Linda, O'connor, Vincent and Dillon, James
(2020)
Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism associated gene.
Human Molecular Genetics, 29 (21), .
(doi:10.1093/hmg/ddaa232).
Abstract
Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism, there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, Caenorhabditis elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms, it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilize this social behaviour to investigate the effect of autism-associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight into complex social behaviour.
Text
Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism-associated gene
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e-pub ahead of print date: 18 November 2020
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© The Author(s) 2020. Published by Oxford University Press. All rights reserved
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Local EPrints ID: 457875
URI: http://eprints.soton.ac.uk/id/eprint/457875
ISSN: 0964-6906
PURE UUID: 157237e0-6770-4d08-a0a6-d044eab824f2
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Date deposited: 21 Jun 2022 18:08
Last modified: 17 Mar 2024 03:32
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Author:
Helena Rawsthorne-Manning
Author:
Emily Feist
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