Functional Transcriptomic Analysis of the Role of MAB-5/Hox in Q Neuroblast Migration in Caenorhabditis Elegans

BMC Genomics. 2013 May 4;14:304. doi: 10.1186/1471-2164-14-304.

Abstract

Background: Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds.

Results: Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration.

Conclusions: Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / physiology
  • Cell Lineage
  • Cell Movement / genetics
  • Chromatin Immunoprecipitation
  • Down-Regulation
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Neural Stem Cells
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • Caenorhabditis elegans Proteins
  • Homeodomain Proteins
  • Mab-5 protein, C elegans
  • Transcription Factors