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Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Schwarz, Erich M. and Kato, Mihoko and Sternberg, Paul W. (2012) Functional transcriptomics of a migrating cell in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 109 (40). pp. 16246-16251. ISSN 0027-8424. PMCID PMC3479585. doi:10.1073/pnas.1203045109.

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In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000– 10,000 genes in the linker cell, 22–25% of which were up- or downregulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.

Item Type:Article
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URLURL TypeDescription CentralArticle
Schwarz, Erich M.0000-0003-3151-4381
Kato, Mihoko0000-0003-3827-8879
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2012 by the National Academy of Sciences. Edited by Ruth Lehmann, New York University Medical Center, New York, NY, and approved August 24, 2012 (received for review February 22, 2012). Published online before print September 18, 2012. We thank M. Goodman, M. Chalfie, and A. Mortazavi for early support in developing single-cell RT-PCR; B. Williams for providing control spike poly(A)+ RNAs; L. Schaeffer, D. Trout, and I. Antoshechkin of the Jacobs Genome Center for Illumina sequencing; A. Narayan for help setting up the dissection rig; J. Downes for scoring linker cell migration phenotypes; J. Thomas for his list of transcription factors; WormBase for gene annotations; and T. Brown, Y.-P. Hsueh, A. Roeder, K. Yook, and A. Zaslaver for comments. This work was supported by National Institutes of Health Grant GM084389 and by the Howard Hughes Medical Institute, with which P.W.S. is an Investigator. Author contributions: E.M.S. and M.K. designed research; E.M.S. and M.K. performed research; E.M.S., M.K., and P.W.S. analyzed data; and E.M.S., M.K., and P.W.S. wrote the paper. The authors declare no conflict of interest.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:major sperm protein; nematode development; transcriptional profiling; twin pore potassium channels; conserved uncharacterized proteins
Issue or Number:40
PubMed Central ID:PMC3479585
Record Number:CaltechAUTHORS:20120924-131548711
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:34313
Deposited By: Tony Diaz
Deposited On:24 Sep 2012 22:23
Last Modified:09 Nov 2021 23:07

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