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Loss of egli-1, the Caenorhabditis elegans Orthologue of a Downstream Target of SMN, Leads to Abnormalities in Sensorimotor Integration

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Abstract

The connectome of Caenorhabditis elegans has been extensively studied and fully mapped, allowing researchers to more confidently conclude on the impact of any change in neuronal circuits based on behavioral data. One of the more complex sensorimotor circuits in nematodes is the one that regulates the integration of feeding status with the subsequent behavioral responses that allow animals to adapt to environmental conditions. Here, we have characterized a Caenorhabditis elegans knockout model of the egli-1 gene (previously known as tag-175). This is an orthologue of the stasimon/tmem41b gene, a downstream target of SMN, the depleted protein in spinal muscular atrophy (SMA), which partially recapitulates the SMA phenotype in fly and zebrafish models when mutated. Surprisingly, egli-1 mutants reveal no deficits in motor function. Instead, they show functional impairment of a specific neuronal circuit, leading to defects in the integration of sensorial information related to food abundance, with consequences at the level of locomotion adaptation, egg laying, and the response to aversive chemical stimuli. This work has demonstrated for the first time the relevance of egli-1 in the nervous system, as well as revealed a function for this gene, which had remained elusive so far.

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Acknowledgments

The authors thank all members of the Maciel lab for helpful tips and discussion; Dr. Anne Hart, Dr. David Sattelle, and Dr. Luísa Pinto for providing helpful technical advice and strains; Dr. Isabel Correia Neves and Dr. Isabel Alonso for providing reagents and RNAi bacterial clones; Dr. Livio Pellizzoni for helpful discussions on gene function; Dr. Tiago Gil Oliveira and Dr. Paula Ludovico for helpful comments on the manuscript; and Ana Marote for valuable help with figure designing.

Funding

This work was supported by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of projects POCI-01-0145-FEDER-007038 and POCI-01-0145-FEDER-031987. Moreover, the work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (project NORTE-01-0145-FEDER-000013). Fellowships supporting the development of this work were attributed by FCT (PD/BD/128074/2016 to J.D.DaS., PD/BD/127818/2016 to S.O., PD/BDE/127834/2016 to J.P-S., SFRH/BPD/102317/2014 to A.T-C., and SFRH/BPD/101925/2014 to M.D.C.). Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

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  1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Jorge Diogo Da Silva, Stéphanie Oliveira, Joana Pereira-Sousa, Andreia Teixeira-Castro, Marta Daniela Costa & Patrícia Maciel

  2. ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Jorge Diogo Da Silva, Stéphanie Oliveira, Joana Pereira-Sousa, Andreia Teixeira-Castro, Marta Daniela Costa & Patrícia Maciel

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Da Silva, J.D., Oliveira, S., Pereira-Sousa, J. et al. Loss of egli-1, the Caenorhabditis elegans Orthologue of a Downstream Target of SMN, Leads to Abnormalities in Sensorimotor Integration. Mol Neurobiol 57, 1553–1569 (2020). https://doi.org/10.1007/s12035-019-01833-0

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