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The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in Caenorhabditis elegans
Ochs, Matthew E. ; Josephson, Matthew P. ; Lundquist, Erik A.
Ochs, Matthew E.
Josephson, Matthew P.
Lundquist, Erik A.
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Abstract
Neuroblast migration is a critical aspect of nervous system development (e.g., neural crest migration). In an unbiased forward genetic screen, we identified a novel player in neuroblast migration, the ETR-1/CELF1 RNA binding protein. CELF1 RNA binding proteins are involved in multiple aspects of RNA processing including alternative splicing, stability, and translation. We find that a specific mutation in alternatively-spliced exon 8 results in migration defects of the AQR and PQR neurons, and not the embryonic lethality and body wall muscle defects of complete knockdown of the locus. Surprisingly, ETR-1 was required in body wall muscle cells for AQR/PQR migration (i.e., it acts cell non-autonomously). Genetic interactions indicate that ETR-1 acts with Wnt signaling, either in the Wnt pathway or in a parallel pathway. Possibly, ETR-1 is involved in the production of a Wnt signal or a parallel signal by the body wall muscles that controls AQR and PQR neuronal migration. In humans, CELF1 is involved in a number of neuromuscular disorders. If the role of ETR-1/CELF1 is conserved, these disorders might also involve cell or neuronal migration. Finally, we describe a technique of amplicon sequencing to detect rare, cell-specific genome edits by CRISPR/Cas9 in vivo (CRISPR-seq) as an alternative to the T7E1 assay.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2020-05-12
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Genetics Society of America
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Keywords
Etr-1, Celf1, C. elegans, Q neuroblast, Migration, CRISPR-seq
Citation
Ochs, M. E., Josephson, M. P., & Lundquist, E. A. (2020). The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in Caenorhabditis elegans. G3 (Bethesda, Md.), 10(7), 2365–2376. https://doi.org/10.1534/g3.120.401182