Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia
Open accessAbstract
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. MZovlmutants 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.
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The function of the primary cilium in fine-tuning WNT signalling remains unclear.
“Thus, despite intense investigation, the function of the primary cilium in fine-tuning WNT signalling remains unclear 204.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [204]
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References 55 · Cited by 210
- Authors
- Huang, P., & Schier, A. F.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Huang, Peng
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-09-15
- Volume
- 136
- Issue
- 18
- Pages
- 3089-3098
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2730366
- OpenAlex
- W1995600594
- Cited by
- 210
- References
- 55
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 6 · 2019: 15 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 8 · 2014: 13 · 2013: 17 · 2012: 27
- FWCI
- 15.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM056211)
- National Institute of Dental and Craniofacial Research (R01DE016779)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Hedgehog signaling, Wnt signaling, cilia, IFT88, zebrafish, SMO, PTC, pKa, Gli1, Wnt/β-catenin signaling, non-canonical Wnt signaling, signal transduction
- MeSH terms
- Zinc Finger Protein GLI1, Animals, Cilia, Epistasis, Genetic, Zebrafish, Signal Transduction, Oncogene Proteins, Trans-Activators, Oligonucleotides, Antisense, In Situ Hybridization, Body Patterning, Zebrafish Proteins, Animals, Genetically Modified, Wnt Proteins, Hedgehog Proteins
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