Hundreds of genes have been implicated in neurodevelopmental disorders. Previous studies have indicated that some phenotypes caused by decreased developmental function of select risk genes can be reversed by restoring gene function in adulthood. However, very few risk genes have been assessed for adult reversibility. We developed a strategy to rapidly assess the temporal requirements and phenotypic reversibility of neurodevelopmental disorder risk gene orthologs using a conditional protein degradation system and machine vision phenotypic profiling in Caenorhabditis elegans. Using this approach, we measured the effects of degrading and re-expressing orthologs of 3 neurodevelopmental risk genes EBF3, BRN3A, and DYNC1H1 across 30 morphological, locomotor, sensory, and learning phenotypes at multiple timepoints throughout development. We found some degree of phenotypic reversibility was possible for each gene studied. However, the temporal requirements of gene function and degree of phenotypic reversibility varied by gene and phenotype, highlighting the critical need of using multiple time windows of degradation and re-expression to understand the many roles a gene can play over developmental time. This work also demonstrates a strategy of using a high-throughput model system to investigate temporal requirements of gene function across a large number of phenotypes to rapidly prioritize neurodevelopmental disorder genes for re-expression studies in other organisms.
Rapid assessment of the temporal function and phenotypic reversibility of neurodevelopmental disorder risk genes in C. elegans
Authors who contributed equally to the work
Currently Viewing Accepted Manuscript - Newer Version Available
- Split-screen
- Views Icon Views
- Open the PDF for in another window
-
Article Versions Icon
Versions
- Version of Record 06 May 2022
- Accepted Manuscript 01 April 2022
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Lexis D. Kepler, Troy A. McDiarmid, Catharine H. Rankin; Rapid assessment of the temporal function and phenotypic reversibility of neurodevelopmental disorder risk genes in C. elegans. Dis Model Mech 2022; dmm.049359. doi: https://doi.org/10.1242/dmm.049359
Download citation file:
Advertisement
Valuing peer review at Disease Models & Mechanisms
We would like to thank our peer reviewers who contributed their time and expertise in 2023. In her latest Editorial, Editor-in-Chief Liz Patton has outlined why we continue to value our peer reviewers dedication.
Subject collection: Building advocacy into research
DMM’s new series - Building advocacy into research - features interviews, ‘The Patient’s Voice’, with patients and advocates for a range of disease types, with the aim of supporting the highest quality research for the benefit of all patients affected by disease.
Travelling Fellowships for early-career researchers
DMM and its sister journals offer Travelling Fellowships of up to £3,000 to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. Find out more about our Travelling Fellowships and read stories from previous grant recipients.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
The Forest of Biologists
Our Publisher Claire Moulton recently visited the two Woodland Trust UK sites where we are planting new native trees for published Research and Review papers and protecting ancient woodland on behalf of our peer reviewers.
Other journals from
The Company of Biologists