The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in<i>Caenorhabditis elegans</i>

Ochs, Matthew; Josephson, Matthew P.; Lundquist, Erik A.

doi:10.1534/g3.120.401182

Cited by 7 publications

(48 citation statements)

References 60 publications

(134 reference statements)

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“…2000), CELF1-6. In C. elegans, there are two CELF genes, etr-1 (most similar to CELF1-2 ) (Milne and Hodgkin 1999; Ochs et al . 2020), and unc-75 (most similar to CELF3-6) (Loria et al .…”

Section: Introductionmentioning

confidence: 99%

“…ETR-1 is involved in muscle development, as knockdown of ETR-1 results in severe muscle disorganization and embryonic lethality (Milne and Hodgkin 1999). ETR-1 also controls cell corpse engulfment in the germline (Boateng and Allen 2018), and influences neuronal migration non-autonomously from body wall muscle (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

“…ETR-1 acts in muscle to guide the long-range migration of the Q neuroblast descendants in C. elegans (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The etr-1(lq61) mutation was isolated in a forward genetic screen for AQR and PQR migration defects (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Total knockdown of etr-1 resulted in embryonic lethality with muscle defects (Milne and Hodgkin 1999), yet etr-1(lq61) animals are viable and fertile, consistent with lq61 being a hypomorphic mutation. etr-1 is expressed in all cells of the embryo (Boateng and Allen 2018), but acts in the muscle cells in a non-autonomous manner to control AQR and PQR migrations (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

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Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

Ochs

McWhirter

Unckless

et al. 2021

Preprint

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Migration of neuroblasts and neurons from their birthplace is central to the formation of neural circuits and networks. ETR-1 is the Caenorhabditis elegans homolog of the CELF1 (CUGBP, ELAV-like family 1) RNA-processing factor involved in neuromuscular disorders. etr-1 regulates body wall muscle differentiation. Our previous work showed that etr-1 in muscle has a non-autonomous role in neuronal migration, suggesting that ETR-1 is involved in the production of a signal emanating from body wall muscle that controls neuroblast migration and that interacts with Wnt signaling. etr-1 is extensively alternatively-spliced, and we identified the viable etr-1(lq61) mutant, caused by a stop codon in alternatively-spliced exon 8 and only affecting etr-1 isoforms containing exon 8. We took advantage of viable etr-1(lq61) to identify potential RNA targets of ETR-1 in body wall muscle using a combination of fluorescence activated cell sorting (FACS) of body wall muscles from wild-type and etr-1(lq61) and subsequent RNA-seq. This analysis revealed genes whose splicing and transcript levels were controlled by ETR-1 exon 8 isoforms, and represented a broad spectrum of genes involved in muscle differentiation, myofilament lattice structure, and physiology. Genes with transcripts underrepresented in etr-1(lq61) included those involved in ribosome function and translation, similar to potential CELF1 targets identified in chick cardiomyocytes. This suggests that at least some targets of ETR-1 might be conserved in vertebrates, and that ETR-1 might generally stimulate translation in muscles. As proof-of-principle, a functional analysis of a subset of ETR-1 targets revealed genes involved in AQR and PQR neuronal migration. One such gene, lev-11/tropomyosin, requires ETR-1 for alternative splicing, and another, unc-52/perlecan, requires ETR-1 for the production of long isoforms containing 3-prime exons. In sum, these studies identified gene targets of ETR-1/CELF1 in muscles, which included genes involved in muscle development and physiology, and genes with novel roles in neuronal migration.

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“…2000), CELF1-6. In C. elegans, there are two CELF genes, etr-1 (most similar to CELF1-2 ) (Milne and Hodgkin 1999; Ochs et al . 2020), and unc-75 (most similar to CELF3-6) (Loria et al .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…ETR-1 acts in muscle to guide the long-range migration of the Q neuroblast descendants in C. elegans (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The etr-1(lq61) mutation was isolated in a forward genetic screen for AQR and PQR migration defects (Ochs et al . 2020).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

Ochs

McWhirter

Unckless

et al. 2021

Preprint

View full text Add to dashboard Cite

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Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development

Rybiczka-Tešulov,

Garritsen,

Venø

et al. 2024

Nat Commun

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The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

Tang

Trivedi

Freund

et al. 2021

Preprint

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The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for specific aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase , although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase . A CATP -8/P5A-ATPase reporter is localized to the ER in most if not all tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific roles in different genetic pathways, and may be involved in the regulation or localization of transmembrane proteins to specific subcellular compartments.

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The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration inCaenorhabditis elegans

Cited by 7 publications

References 60 publications

Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration

Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

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