Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish.
BACKGROUND
In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh) signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish.


RESULTS
Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation.


CONCLUSIONS
Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.
Kim
Hyejeong Rosemary
HR
MRC Centre for Developmental & Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, UK.
Richardson
Joanna
J
van Eeden
Freek
F
Ingham
Philip W
PW
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002923:Cilia / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2
D002352:Carrier Proteins; D017931:DNA Primers; C488008:Dzip1 protein, zebrafish; D053823:Hedgehog Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000075746:Zinc Finger Protein Gli2; C118355:gli2a protein, zebrafish; D049452:Green Fluorescent Proteins