Roles of hedgehog pathway components and retinoic acid signalling in specifying zebrafish ventral spinal cord neurons

Samantha England, Manuel F. Batista, John K. Mich, James K. Chen, Katharine E. Lewis

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

SUMMARY In mouse, Hedgehog (Hh) signalling is required for most ventral spinal neurons to form. Here, we analyse the spinal cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signalling. We find that most V3 domain cells and motoneurons are lost, whereas medial floorplate still develops normally and V2, V1 and V0v cells form in normal numbers. This phenotype resembles that of mice that lack both Hh signalling and Gli repressor activity. Ventral spinal cord progenitor domain transcription factors are not expressed at 24 hpf in zebrafish MZsmo mutants. However, pMN, p2 and p1 domain markers are expressed at early somitogenesis stages in these mutants. This suggests that Gli repressor activity does not extend into zebrafish ventral spinal cord at these stages, even in the absence of Hh signalling. Consistent with this, ectopic expression of Gli3R represses ventral progenitor domain expression at these early stages and knocking down Gli repressor activity rescues later expression. We investigated whether retinoic acid (RA) signalling specifies ventral spinal neurons in the absence of Hh signalling. The results suggest that RA is required for the correct number of many different spinal neurons to form. This is probably mediated, in part, by an effect on cell proliferation. However, V0v, V1 and V2 cells are still present, even in the absence of both Hh and RA signalling. We demonstrate that Gli1 has a Hh-independent role in specifying most of the remaining motoneurons and V3 domain cells in embryos that lack Hh signalling, but removal of Gli1 activity does not affect more dorsal neurons.

Original languageEnglish (US)
Pages (from-to)5121-5134
Number of pages14
JournalDevelopment
Volume138
Issue number23
DOIs
StatePublished - Dec 1 2011

Keywords

  • Floor plate
  • Gli3
  • Interneuron
  • Smoothened
  • V1
  • V2
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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