Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Development 136 (18): 3089-3098

Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia

Peng Huang*, and Alexander F. Schier*

Department of Molecular and Cellular Biology, Center for Brain Science, Harvard Stem Cell Institute, Broad Institute, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

* Authors for correspondence (huang{at}mcb.harvard.edu; schier{at}fas.harvard.edu)

Accepted for publication 22 July 2009.

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.

Key Words: Cilia • Hedgehog signaling • Wnt signaling • Gli • Spinal cord • Somite • Zebrafish


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hedgehog Signaling Requires Motile Cilia in the Sea Urchin.
J. F. Warner, A. M. McCarthy, R. L. Morris, and D. R. McClay (2014)
Mol. Biol. Evol. 31, 18-22
   Abstract »    Full Text »    PDF »
Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish.
X. Wang, Z. Zhao, J. Muller, A. Iyu, A. J. Khng, E. Guccione, Y. Ruan, and P. W. Ingham (2013)
Biology Open 2, 1203-1213
   Abstract »    Full Text »    PDF »
Primary cilia and kidney injury: current research status and future perspectives.
S. Wang and Z. Dong (2013)
Am J Physiol Renal Physiol 305, F1085-F1098
   Abstract »    Full Text »    PDF »
Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects.
Z. A. Abdelhamed, G. Wheway, K. Szymanska, S. Natarajan, C. Toomes, C. Inglehearn, and C. A. Johnson (2013)
Hum. Mol. Genet. 22, 1358-1372
   Abstract »    Full Text »    PDF »
Context-Dependent Regulation of Wnt Signaling through the Primary Cilium.
E. C. Oh and N. Katsanis (2013)
J. Am. Soc. Nephrol. 24, 10-18
   Abstract »    Full Text »    PDF »
miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish.
C. Stahlhut, Y. Suarez, J. Lu, Y. Mishima, and A. J. Giraldez (2012)
Development 139, 4356-4365
   Abstract »    Full Text »    PDF »
Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity.
A. Mahuzier, H.-M. Gaude, V. Grampa, I. Anselme, F. Silbermann, M. Leroux-Berger, D. Delacour, J. Ezan, M. Montcouquiol, S. Saunier, et al. (2012)
J. Cell Biol. 198, 927-940
   Abstract »    Full Text »    PDF »
The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle.
G. A. Stooke-Vaughan, P. Huang, K. L. Hammond, A. F. Schier, and T. T. Whitfield (2012)
Development 139, 1777-1787
   Abstract »    Full Text »    PDF »
BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes.
Q. Zhang, S. Seo, K. Bugge, E. M. Stone, and V. C. Sheffield (2012)
Hum. Mol. Genet. 21, 1945-1953
   Abstract »    Full Text »    PDF »
Cilia in vertebrate development and disease.
E. C. Oh and N. Katsanis (2012)
Development 139, 443-448
   Abstract »    Full Text »    PDF »
Wnt/{beta}-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer's vesicle.
A. Caron, X. Xu, and X. Lin (2012)
Development 139, 514-524
   Abstract »    Full Text »    PDF »
Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish.
J. K. Mich and J. K. Chen (2011)
Development 138, 5113-5119
   Abstract »    Full Text »    PDF »
Roles of Hedgehog pathway components and retinoic acid signalling in specifying zebrafish ventral spinal cord neurons.
S. England, M. F. Batista, J. K. Mich, J. K. Chen, and K. E. Lewis (2011)
Development 138, 5121-5134
   Abstract »    Full Text »    PDF »
Targeted mutation of the talpid3 gene in zebrafish reveals its conserved requirement for ciliogenesis and Hedgehog signalling across the vertebrates.
J. Ben, S. Elworthy, A. S. M. Ng, F. van Eeden, and P. W. Ingham (2011)
Development 138, 4969-4978
   Abstract »    Full Text »    PDF »
Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms.
C. W. Sipe and X. Lu (2011)
Development 138, 3441-3449
   Abstract »    Full Text »    PDF »
Growth Arrest Specific 8 (Gas8) and G Protein-coupled Receptor Kinase 2 (GRK2) Cooperate in the Control of Smoothened Signaling.
T. Evron, M. Philipp, J. Lu, A. R. Meloni, M. Burkhalter, W. Chen, and M. G. Caron (2011)
J. Biol. Chem. 286, 27676-27686
   Abstract »    Full Text »    PDF »
Principles of planar polarity in animal development.
L. V. Goodrich and D. Strutt (2011)
Development 138, 1877-1892
   Abstract »    Full Text »    PDF »
N-cadherin-mediated cell adhesion restricts cell proliferation in the dorsal neural tube.
K. Chalasani and R. M. Brewster (2011)
Mol. Biol. Cell 22, 1505-1515
   Abstract »    Full Text »    PDF »
Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear.
X. Yu, D. Lau, C. P. Ng, and S. Roy (2011)
Development 138, 487-494
   Abstract »    Full Text »    PDF »
Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia.
J. B. Wallingford and B. Mitchell (2011)
Genes & Dev. 25, 201-213
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXX. The Class Frizzled Receptors.
G. Schulte (2010)
Pharmacol. Rev. 62, 632-667
   Abstract »    Full Text »    PDF »
Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif-containing Proteins C10orf90 and KIAA1731.
V. J. Knorz, C. Spalluto, M. Lessard, T. L. Purvis, F. F. Adigun, G. B. Collin, N. A. Hanley, D. I. Wilson, and T. Hearn (2010)
Mol. Biol. Cell 21, 3617-3629
   Abstract »    Full Text »    PDF »
More than Maintenance? A Role for IFT Genes in Planar Cell Polarity.
K. M. Jaffe and R. D. Burdine (2010)
J. Am. Soc. Nephrol. 21, 1240-1241
   Full Text »    PDF »
Intraflagellar Transport Proteins Are Essential for Cilia Formation and for Planar Cell Polarity.
Y. Cao, A. Park, and Z. Sun (2010)
J. Am. Soc. Nephrol. 21, 1326-1333
   Abstract »    Full Text »    PDF »
The Intraflagellar Transport Protein Ift80 Is Essential for Photoreceptor Survival in a Zebrafish Model of Jeune Asphyxiating Thoracic Dystrophy.
L. M. Hudak, S. Lunt, C.-H. Chang, E. Winkler, H. Flammer, M. Lindsey, and B. D. Perkins (2010)
Invest. Ophthalmol. Vis. Sci. 51, 3792-3799
   Abstract »    Full Text »    PDF »
Mechanism and evolution of cytosolic Hedgehog signal transduction.
C. W. Wilson and P.-T. Chuang (2010)
Development 137, 2079-2094
   Abstract »    Full Text »    PDF »
Bardet-Biedl Syndrome-associated Small GTPase ARL6 (BBS3) Functions at or near the Ciliary Gate and Modulates Wnt Signaling.
C. J. Wiens, Y. Tong, M. A. Esmail, E. Oh, J. M. Gerdes, J. Wang, W. Tempel, J. B. Rattner, N. Katsanis, H. W. Park, et al. (2010)
J. Biol. Chem. 285, 16218-16230
   Abstract »    Full Text »    PDF »
Cilia Organize Ependymal Planar Polarity.
Z. Mirzadeh, Y.-G. Han, M. Soriano-Navarro, J. M. Garcia-Verdugo, and A. Alvarez-Buylla (2010)
J. Neurosci. 30, 2600-2610
   Abstract »    Full Text »    PDF »
Planarian Hh Signaling Regulates Regeneration Polarity and Links Hh Pathway Evolution to Cilia.
J. C. Rink, K. A. Gurley, S. A. Elliott, and A. Sanchez Alvarado (2009)
Science 326, 1406-1410
   Abstract »    Full Text »    PDF »
Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion.
N. A. Duldulao, S. Lee, and Z. Sun (2009)
Development 136, 4033-4042
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882