Functional transcriptomics of a migrating cell in Caenorhabditis elegans

Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16246-51. doi: 10.1073/pnas.1203045109. Epub 2012 Sep 18.

Abstract

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 down-regulated 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development*
  • Cell Movement / genetics*
  • Cell Movement / physiology
  • Gene Expression Regulation, Developmental / physiology*
  • Gonads / cytology*
  • Larva / physiology
  • Male
  • Organogenesis / physiology*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome / genetics*