Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia

Development. 2009 Sep;136(18):3089-98. doi: 10.1242/dev.041343.

Abstract

Cilia have been implicated in Hedgehog (Hh) and Wnt signaling in mouse but not in Drosophila. To determine whether the role of cilia is conserved in zebrafish, we generated maternal-zygotic (MZ) oval (ovl; ift88) mutants that lack all cilia. MZovl mutants display normal canonical and non-canonical Wnt signaling but show defects in Hh signaling. As in mouse, zebrafish cilia are required to mediate the activities of Hh, Ptc, Smo and PKA. However, in contrast to mouse Ift88 mutants, which show a dramatic reduction in Hh signaling, zebrafish MZovl mutants display dampened, but expanded, Hh pathway activity. This activity is largely due to gli1, the expression of which is fully dependent on Hh signaling in mouse but not in zebrafish. These results reveal a conserved requirement for cilia in transducing the activity of upstream regulators of Hh signaling but distinct phenotypic effects due to differential regulation and differing roles of transcriptional mediators.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Cilia / metabolism*
  • Epistasis, Genetic
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • In Situ Hybridization
  • Oligonucleotides, Antisense
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • Zebrafish* / anatomy & histology
  • Zebrafish* / embryology
  • Zebrafish* / metabolism
  • Zinc Finger Protein GLI1

Substances

  • Hedgehog Proteins
  • Oligonucleotides, Antisense
  • Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • Zinc Finger Protein GLI1