The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding

Anna Y. Zinovyeva, Serena M. Graham, Veronica J. Cloud, Wayne C. Forrester

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Histone proteins play integral roles in chromatin structure and function. Histones are subject to several types of posttranslational modifications, including acetylation, which can produce transcriptional activation. The converse, histone deacetylation, is mediated by histone deacetylases (HDACs) and often is associated with transcriptional silencing. We identified a new mutation, cw2, in the Caenorhabditis elegans hda-1 gene, which encodes a histone deacetylase. Previous studies showed that a mutation in hda-1, e1795, or reduction of hda-1 RNA by RNAi causes defective vulval and gonadal development leading to sterility. The hda-1(cw2) mutation causes defective vulval development and reduced fertility, like hda-1(e1795), albeit with reduced severity. Unlike the previously reported hda-1 mutation, hda-1(cw2) mutants are viable as homozygotes, although many die as embryos or larvae, and are severely uncoordinated. Strikingly, in hda-1(cw2) mutants, axon pathfinding is defective; specific axons often appear to wander randomly or migrate in the wrong direction. In addition, the long range migrations of three neuron types and fasciculation of the ventral nerve cord are defective. Together, our studies define a new role for HDA-1 in nervous system development, and provide the first evidence for HDAC function in regulating neuronal axon guidance.

Original languageEnglish (US)
Pages (from-to)229-242
Number of pages14
JournalDevelopmental Biology
Volume289
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Axon pathfinding
  • Cell migration
  • hda-1
  • Histone deacetylase

ASJC Scopus subject areas

  • Developmental Biology

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