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

Science 317 (5836): 372-376

Copyright © 2007 by the American Association for the Advancement of Science

Patched1 Regulates Hedgehog Signaling at the Primary Cilium

Rajat Rohatgi,1,2* Ljiljana Milenkovic,1* Matthew P. Scott1{dagger}

Abstract: Primary cilia are essential for transduction of the Hedgehog (Hh) signal in mammals. We investigated the role of primary cilia in regulation of Patched1 (Ptc1), the receptor for Sonic Hedgehog (Shh). Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia. When Shh bound to Ptc1, Ptc1 left the cilia, leading to accumulation of Smo and activation of signaling. Thus, primary cilia sense Shh and transduce signals that play critical roles in development, carcinogenesis, and stem cell function.

1 Departments of Developmental Biology, Genetics, and Bioengineering and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: mscott{at}stanford.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts Is Essential for High Hedgehog Activity Transduction.
D. Shi, X. Lv, Z. Zhang, X. Yang, Z. Zhou, L. Zhang, and Y. Zhao (2013)
J. Biol. Chem. 288, 12605-12614
   Abstract »    Full Text »    PDF »
Discovery, Molecular and Pharmacological Characterization of GSA-10, a Novel Small-Molecule Positive Modulator of Smoothened.
T. Gorojankina, L. Hoch, H. Faure, H. Roudaut, E. Traiffort, A. Schoenfelder, N. Girard, A. Mann, F. Manetti, A. Solinas, et al. (2013)
Mol. Pharmacol. 83, 1020-1029
   Abstract »    Full Text »    PDF »
Kif3a is necessary for initiation and maintenance of medulloblastoma.
M. T. Barakat, E. W. Humke, and M. P. Scott (2013)
Carcinogenesis
   Abstract »    Full Text »    PDF »
The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia.
J. A. Caparros-Martin, M. Valencia, E. Reytor, M. Pacheco, M. Fernandez, A. Perez-Aytes, E. Gean, P. Lapunzina, H. Peters, J. A. Goodship, et al. (2013)
Hum. Mol. Genet. 22, 124-139
   Abstract »    Full Text »    PDF »
Temporal deletion of Arl13b reveals that a mispatterned neural tube corrects cell fate over time.
C.-Y. Su, S. N. Bay, L. E. Mariani, M. J. Hillman, and T. Caspary (2012)
Development 139, 4062-4071
   Abstract »    Full Text »    PDF »
The Hedgehog Receptor Patched Functions in Multidrug Transport and Chemotherapy Resistance.
M. Bidet, A. Tomico, P. Martin, H. Guizouarn, P. Mollat, and I. Mus-Veteau (2012)
Mol. Cancer Res. 10, 1496-1508
   Abstract »    Full Text »    PDF »
The Hedgehog Signal Transduction Network.
D. J. Robbins, D. L. Fei, and N. A. Riobo (2012)
Science Signaling 5, re6
   Abstract »    Full Text »    PDF »
Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons.
N. Mitchell, R. S. Petralia, D. G. Currier, Y.-X. Wang, A. Kim, M. P. Mattson, and P. J. Yao (2012)
J. Cell Sci. 125, 4207-4213
   Abstract »    Full Text »    PDF »
Hedgehog-Stimulated Chemotaxis Is Mediated by Smoothened Located Outside the Primary Cilium.
M. F. Bijlsma, H. Damhofer, and H. Roelink (2012)
Science Signaling 5, ra60
   Abstract »    Full Text »    PDF »
Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.
V. M. Wu, S. C. Chen, M. R. Arkin, and J. F. Reiter (2012)
PNAS 109, 13644-13649
   Abstract »    Full Text »    PDF »
Characterization of an apical ceramide-enriched compartment regulating ciliogenesis.
Q. He, G. Wang, S. Dasgupta, M. Dinkins, G. Zhu, and E. Bieberich (2012)
Mol. Biol. Cell 23, 3156-3166
   Abstract »    Full Text »    PDF »
Targeting the Sonic Hedgehog Pathway in Keratocystic Odontogenic Tumor.
C. Ren, H. M. Amm, P. DeVilliers, Y. Wu, J. R. Deatherage, Z. Liu, and M. MacDougall (2012)
J. Biol. Chem. 287, 27117-27125
   Abstract »    Full Text »    PDF »
Scoring a backstage pass: Mechanisms of ciliogenesis and ciliary access.
F. R. Garcia-Gonzalo and J. F. Reiter (2012)
J. Cell Biol. 197, 697-709
   Abstract »    Full Text »    PDF »
Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop.
W.-M. Woo, H. H. Zhen, and A. E. Oro (2012)
Genes & Dev. 26, 1235-1246
   Abstract »    Full Text »    PDF »
Hedgehog Secretion and Signal Transduction in Vertebrates.
K. E. Ryan and C. Chiang (2012)
J. Biol. Chem. 287, 17905-17913
   Abstract »    Full Text »    PDF »
Orchestrating transcriptional control of adult neurogenesis.
J. Hsieh (2012)
Genes & Dev. 26, 1010-1021
   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 »
Molecular Pathways: The Role of Primary Cilia in Cancer Progression and Therapeutics with a Focus on Hedgehog Signaling.
N. B. Hassounah, T. A. Bunch, and K. M. McDermott (2012)
Clin. Cancer Res. 18, 2429-2435
   Abstract »    Full Text »    PDF »
Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies.
A. Ashe, N. C. Butterfield, L. Town, A. D. Courtney, A. N. Cooper, C. Ferguson, R. Barry, F. Olsson, K. F. Liem Jr, R. G. Parton, et al. (2012)
Hum. Mol. Genet. 21, 1808-1823
   Abstract »    Full Text »    PDF »
Targeting hedgehog in hematologic malignancy.
D. A. Irvine and M. Copland (2012)
Blood 119, 2196-2204
   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 »
The extracellular loops of Smoothened play a regulatory role in control of Hedgehog pathway activation.
C. E. Carroll, S. Marada, D. P. Stewart, J. X. Ouyang, and S. K. Ogden (2012)
Development 139, 612-621
   Abstract »    Full Text »    PDF »
Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins.
C. E. Larkins, G. D. G. Aviles, M. P. East, R. A. Kahn, and T. Caspary (2011)
Mol. Biol. Cell 22, 4694-4703
   Abstract »    Full Text »    PDF »
Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube.
M. Tuson, M. He, and K. V. Anderson (2011)
Development 138, 4921-4930
   Abstract »    Full Text »    PDF »
Neuropilins are positive regulators of Hedgehog signal transduction.
R. T. Hillman, B. Y. Feng, J. Ni, W.-M. Woo, L. Milenkovic, M. G. Hayden Gephart, M. N. Teruel, A. E. Oro, J. K. Chen, and M. P. Scott (2011)
Genes & Dev. 25, 2333-2346
   Abstract »    Full Text »    PDF »
Scrutinizing ciliopathies by unraveling ciliary interaction networks.
J. van Reeuwijk, H. H. Arts, and R. Roepman (2011)
Hum. Mol. Genet. 20, R149-R157
   Abstract »    Full Text »    PDF »
A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus.
J. M. Friedland-Little, A. D. Hoffmann, P. J. R. Ocbina, M. A. Peterson, J. D. Bosman, Y. Chen, S. Y. Cheng, K. V. Anderson, and I. P. Moskowitz (2011)
Hum. Mol. Genet. 20, 3725-3737
   Abstract »    Full Text »    PDF »
Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei.
M. Oberholzer, G. Langousis, H. T. Nguyen, E. A. Saada, M. M. Shimogawa, Z. O. Jonsson, S. M. Nguyen, J. A. Wohlschlegel, and K. L. Hill (2011)
Mol. Cell. Proteomics 10, M111.010538
   Abstract »    Full Text »    PDF »
Primary Cilia Regulate Proliferation of Amplifying Progenitors in Adult Hippocampus: Implications for Learning and Memory.
A. Amador-Arjona, J. Elliott, A. Miller, A. Ginbey, G. J. Pazour, G. Enikolopov, A. J. Roberts, and A. V. Terskikh (2011)
J. Neurosci. 31, 9933-9944
   Abstract »    Full Text »    PDF »
Heterotrimeric Gi Proteins Link Hedgehog Signaling to Activation of Rho Small GTPases to Promote Fibroblast Migration.
A. H. Polizio, P. Chinchilla, X. Chen, S. Kim, D. R. Manning, and N. A. Riobo (2011)
J. Biol. Chem. 286, 19589-19596
   Abstract »    Full Text »    PDF »
Dual Phosphorylation of Suppressor of Fused (Sufu) by PKA and GSK3{beta} Regulates Its Stability and Localization in the Primary Cilium.
Y. Chen, S. Yue, L. Xie, X.-h. Pu, T. Jin, and S. Y. Cheng (2011)
J. Biol. Chem. 286, 13502-13511
   Abstract »    Full Text »    PDF »
Sonic Hedgehog Stimulates Proliferation of Human Periodontal Ligament Stem Cells.
C. Martinez, P. C. Smith, J. P. Rodriguez, and V. Palma (2011)
Journal of Dental Research 90, 483-488
   Abstract »    PDF »
Disease and animal research: a meeting review.
L. V. Sun (2011)
J Mol Cell Biol 3, 78-80
   Full Text »    PDF »
PTHrP Treatment Fails to Rescue Bone Defects Caused by Hedgehog Pathway Inhibition in Young Mice.
J. L. Brechbiel, J. M. Y. Ng, and T. Curran (2011)
Toxicol Pathol 39, 478-485
   Abstract »    Full Text »    PDF »
Functional characterization of putative cilia genes by high-content analysis.
C. K. Lai, N. Gupta, X. Wen, L. Rangell, B. Chih, A. S. Peterson, J. F. Bazan, L. Li, and S. J. Scales (2011)
Mol. Biol. Cell 22, 1104-1119
   Abstract »    Full Text »    PDF »
Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord.
Y. H. Belgacem and L. N. Borodinsky (2011)
PNAS 108, 4482-4487
   Abstract »    Full Text »    PDF »
Sonic Hedgehog-induced Proliferation Requires Specific Gα Inhibitory Proteins.
M. Barzi, D. Kostrz, A. Menendez, and S. Pons (2011)
J. Biol. Chem. 286, 8067-8074
   Abstract »    Full Text »    PDF »
Identification and Mechanism of Action of the Acylguanidine MRT-83, a Novel Potent Smoothened Antagonist.
H. Roudaut, E. Traiffort, T. Gorojankina, L. Vincent, H. Faure, A. Schoenfelder, A. Mann, F. Manetti, A. Solinas, M. Taddei, et al. (2011)
Mol. Pharmacol. 79, 453-460
   Abstract »    Full Text »    PDF »
Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling.
F. Li, W. Shi, M. Capurro, and J. Filmus (2011)
J. Cell Biol. 192, 691-704
   Abstract »    Full Text »    PDF »
Genome-Wide RNAi Screen Reveals Disease-Associated Genes That Are Common to Hedgehog and Wnt Signaling.
L. S. Jacob, X. Wu, M. E. Dodge, C.-W. Fan, O. Kulak, B. Chen, W. Tang, B. Wang, J. F. Amatruda, and L. Lum (2011)
Science Signaling 4, ra4
   Abstract »    Full Text »    PDF »
Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components.
J. Qin, Y. Lin, R. X. Norman, H. W. Ko, and J. T. Eggenschwiler (2011)
PNAS 108, 1456-1461
   Abstract »    Full Text »    PDF »
Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome.
C. Cui, B. Chatterjee, D. Francis, Q. Yu, J. T. SanAgustin, R. Francis, T. Tansey, C. Henry, B. Wang, B. Lemley, et al. (2011)
Dis. Model. Mech. 4, 43-56
   Abstract »    Full Text »    PDF »
Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling.
C. Cruz, V. Ribes, E. Kutejova, J. Cayuso, V. Lawson, D. Norris, J. Stevens, M. Davey, K. Blight, F. Bangs, et al. (2010)
Development 137, 4271-4282
   Abstract »    Full Text »    PDF »
A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.
H. Tukachinsky, L. V. Lopez, and A. Salic (2010)
J. Cell Biol. 191, 415-428
   Abstract »    Full Text »    PDF »
Interactions between Hedgehog proteins and their binding partners come into view.
P. A. Beachy, S. G. Hymowitz, R. A. Lazarus, D. J. Leahy, and C. Siebold (2010)
Genes & Dev. 24, 2001-2012
   Abstract »    Full Text »    PDF »
Frequent Deregulations in the Hedgehog Signaling Network and Cross-Talks with the Epidermal Growth Factor Receptor Pathway Involved in Cancer Progression and Targeted Therapies.
M. Mimeault and S. K. Batra (2010)
Pharmacol. Rev. 62, 497-524
   Abstract »    Full Text »    PDF »
Rab10 associates with primary cilia and the exocyst complex in renal epithelial cells.
C. M. Babbey, R. L. Bacallao, and K. W. Dunn (2010)
Am J Physiol Renal Physiol 299, F495-F506
   Abstract »    Full Text »    PDF »
Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes.
M. Kalogeropoulos, S. S. Varanasi, O. K. Olstad, P. Sanderson, V. T. Gautvik, S. Reppe, R. M. Francis, K. M. Gautvik, M. A. Birch, and H. K. Datta (2010)
FASEB J 24, 2893-2903
   Abstract »    Full Text »    PDF »
Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells.
R. Y. Kwon, S. Temiyasathit, P. Tummala, C. C. Quah, and C. R. Jacobs (2010)
FASEB J 24, 2859-2868
   Abstract »    Full Text »    PDF »
Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector.
J. Kim, J. J. Lee, J. Kim, D. Gardner, and P. A. Beachy (2010)
PNAS 107, 13432-13437
   Abstract »    Full Text »    PDF »
A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution.
Q. Hu, L. Milenkovic, H. Jin, M. P. Scott, M. V. Nachury, E. T. Spiliotis, and W. J. Nelson (2010)
Science 329, 436-439
   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 »
Targeting Hedgehog -- a Cancer Stem Cell Pathway.
A. A. Merchant and W. Matsui (2010)
Clin. Cancer Res. 16, 3130-3140
   Abstract »    Full Text »    PDF »
Differential role of Rab proteins in ciliary trafficking: Rab23 regulates Smoothened levels.
C. Boehlke, M. Bashkurov, A. Buescher, T. Krick, A.-K. John, R. Nitschke, G. Walz, and E. W. Kuehn (2010)
J. Cell Sci. 123, 1460-1467
   Abstract »    Full Text »    PDF »
Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer.
A. Slusarz, N. S. Shenouda, M. S. Sakla, S. K. Drenkhahn, A. S. Narula, R. S. MacDonald, C. L. Besch-Williford, and D. B. Lubahn (2010)
Cancer Res. 70, 3382-3390
   Abstract »    Full Text »    PDF »
A primary cilia-dependent etiology for midline facial disorders.
S. A. Brugmann, N. C. Allen, A. W. James, Z. Mekonnen, E. Madan, and J. A. Helms (2010)
Hum. Mol. Genet. 19, 1577-1592
   Abstract »    Full Text »    PDF »
Kinetics of Hedgehog-Dependent Full-Length Gli3 Accumulation in Primary Cilia and Subsequent Degradation.
X. Wen, C. K. Lai, M. Evangelista, J.-A. Hongo, F. J. de Sauvage, and S. J. Scales (2010)
Mol. Cell. Biol. 30, 1910-1922
   Abstract »    Full Text »    PDF »
Not Lost in Space: Trafficking in the Hedgehog Signaling Pathway.
L. Milenkovic and M. P. Scott (2010)
Science Signaling 3, pe14
   Abstract »    Full Text »    PDF »
The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins.
E. W. Humke, K. V. Dorn, L. Milenkovic, M. P. Scott, and R. Rohatgi (2010)
Genes & Dev. 24, 670-682
   Abstract »    Full Text »    PDF »
Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.
M. Barzi, J. Berenguer, A. Menendez, R. Alvarez-Rodriguez, and S. Pons (2010)
J. Cell Sci. 123, 62-69
   Abstract »    Full Text »    PDF »
Evidence for a role of vertebrate Disp1 in long-range Shh signaling.
L. A. Etheridge, T. Q. Crawford, S. Zhang, and H. Roelink (2010)
Development 137, 133-140
   Abstract »    Full Text »    PDF »
Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus.
J. Kim, M. Kato, and P. A. Beachy (2009)
PNAS 106, 21666-21671
   Abstract »    Full Text »    PDF »
Patched regulates Smoothened trafficking using lipoprotein-derived lipids.
H. Khaliullina, D. Panakova, C. Eugster, F. Riedel, M. Carvalho, and S. Eaton (2009)
Development 136, 4111-4121
   Abstract »    Full Text »    PDF »
A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling.
S. D. Weatherbee, L. A. Niswander, and K. V. Anderson (2009)
Hum. Mol. Genet. 18, 4565-4575
   Abstract »    Full Text »    PDF »
Cystin, Cilia, and Cysts: Unraveling Trafficking Determinants.
T. W. Hurd and B. Margolis (2009)
J. Am. Soc. Nephrol. 20, 2485-2486
   Full Text »    PDF »
The Rfx4 Transcription Factor Modulates Shh Signaling by Regional Control of Ciliogenesis.
A. M. Ashique, Y. Choe, M. Karlen, S. R. May, K. Phamluong, M. J. Solloway, J. Ericson, and A. S. Peterson (2009)
Science Signaling 2, ra70
   Abstract »    Full Text »    PDF »
Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.
L. Milenkovic, M. P. Scott, and R. Rohatgi (2009)
J. Cell Biol. 187, 365-374
   Abstract »    Full Text »    PDF »
The subependymal zone neurogenic niche: a beating heart in the centre of the brain: How plastic is adult neurogenesis? Opportunities for therapy and questions to be addressed.
I. Kazanis (2009)
Brain 132, 2909-2921
   Abstract »    Full Text »    PDF »
Regulation of primary cilia formation by ceramide.
G. Wang, K. Krishnamurthy, and E. Bieberich (2009)
J. Lipid Res. 50, 2103-2110
   Abstract »    Full Text »    PDF »
Negative Regulation of Hedgehog Signaling by Liver X Receptors.
W.-K. Kim, V. Meliton, K. W. Park, C. Hong, P. Tontonoz, P. Niewiadomski, J. A. Waschek, S. Tetradis, and F. Parhami (2009)
Mol. Endocrinol. 23, 1532-1543
   Abstract »    Full Text »    PDF »
Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia.
P. Huang and A. F. Schier (2009)
Development 136, 3089-3098
   Abstract »    Full Text »    PDF »
The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation.
C. A. Clement, S. G. Kristensen, K. Mollgard, G. J. Pazour, B. K. Yoder, L. A. Larsen, and S. T. Christensen (2009)
J. Cell Sci. 122, 3070-3082
   Abstract »    Full Text »    PDF »
Planar Cell Polarity Signaling: The Developing Cell's Compass.
E. K. Vladar, D. Antic, and J. D. Axelrod (2009)
Cold Spring Harb Perspect Biol 1, a002964
   Abstract »    Full Text »    PDF »
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade.
J. M. Hyman, A. J. Firestone, V. M. Heine, Y. Zhao, C. A. Ocasio, K. Han, M. Sun, P. G. Rack, S. Sinha, J. J. Wu, et al. (2009)
PNAS 106, 14132-14137
   Abstract »    Full Text »    PDF »
Variations in Hedgehog signaling: divergence and perpetuation in Sufu regulation of Gli.
L. Ruel and P. P. Therond (2009)
Genes & Dev. 23, 1843-1848
   Abstract »    Full Text »    PDF »
Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved.
M.-H. Chen, C. W. Wilson, Y.-J. Li, K. K. L. Law, C.-S. Lu, R. Gacayan, X. Zhang, C.-c. Hui, and P.-T. Chuang (2009)
Genes & Dev. 23, 1910-1928
   Abstract »    Full Text »    PDF »
Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling.
K. F. Liem Jr, M. He, P. J. R. Ocbina, and K. V. Anderson (2009)
PNAS 106, 13377-13382
   Abstract »    Full Text »    PDF »
Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes.
D. Zhu, S. Shi, H. Wang, and K. Liao (2009)
J. Cell Sci. 122, 2760-2768
   Abstract »    Full Text »    PDF »
Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling.
R. X. Norman, H. W. Ko, V. Huang, C. M. Eun, L. L. Abler, Z. Zhang, X. Sun, and J. T. Eggenschwiler (2009)
Hum. Mol. Genet. 18, 1740-1754
   Abstract »    Full Text »    PDF »
Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway.
V. L. Patterson, C. Damrau, A. Paudyal, B. Reeve, D. T. Grimes, M. E. Stewart, D. J. Williams, P. Siggers, A. Greenfield, and J. N. Murdoch (2009)
Hum. Mol. Genet. 18, 1719-1739
   Abstract »    Full Text »    PDF »
Primary cilia regulate Shh activity in the control of molar tooth number.
A. Ohazama, C. J. Haycraft, M. Seppala, J. Blackburn, S. Ghafoor, M. Cobourne, D. C. Martinelli, C.-M. Fan, R. Peterkova, H. Lesot, et al. (2009)
Development 136, 897-903
   Abstract »    Full Text »    PDF »
Hedgehog signal transduction by Smoothened: Pharmacologic evidence for a 2-step activation process.
R. Rohatgi, L. Milenkovic, R. B. Corcoran, and M. P. Scott (2009)
PNAS 106, 3196-3201
   Abstract »    Full Text »    PDF »
Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation.
Y. Wang, Z. Zhou, C. T. Walsh, and A. P. McMahon (2009)
PNAS 106, 2623-2628
   Abstract »    Full Text »    PDF »
The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation.
Y. Yin, F. Bangs, I. R. Paton, A. Prescott, J. James, M. G. Davey, P. Whitley, G. Genikhovich, U. Technau, D. W. Burt, et al. (2009)
Development 136, 655-664
   Abstract »    Full Text »    PDF »
Characterization of PKD Protein-Positive Exosome-Like Vesicles.
M. C. Hogan, L. Manganelli, J. R. Woollard, A. I. Masyuk, T. V. Masyuk, R. Tammachote, B. Q. Huang, A. A. Leontovich, T. G. Beito, B. J. Madden, et al. (2009)
J. Am. Soc. Nephrol. 20, 278-288
   Abstract »    Full Text »    PDF »
Pancreatic Cancer and Precursor Pancreatic Intraepithelial Neoplasia Lesions Are Devoid of Primary Cilia.
E. S. Seeley, C. Carriere, T. Goetze, D. S. Longnecker, and M. Korc (2009)
Cancer Res. 69, 422-430
   Abstract »    Full Text »    PDF »
C2cd3 is required for cilia formation and Hedgehog signaling in mouse.
A. N. Hoover, A. Wynkoop, H. Zeng, J. Jia, L. A. Niswander, and A. Liu (2008)
Development 135, 4049-4058
   Abstract »    Full Text »    PDF »
Smoothened Signaling in Vertebrates Is Facilitated by a G Protein-coupled Receptor Kinase.
M. Philipp, G. B. Fralish, A. R. Meloni, W. Chen, A. W. MacInnes, L. S. Barak, and M. G. Caron (2008)
Mol. Biol. Cell 19, 5478-5489
   Abstract »    Full Text »    PDF »
Kinome siRNA Screen Identifies Regulators of Ciliogenesis and Hedgehog Signal Transduction.
M. Evangelista, T. Y. Lim, J. Lee, L. Parker, A. Ashique, A. S. Peterson, W. Ye, D. P. Davis, and F. J. de Sauvage (2008)
Science Signaling 1, ra7
   Abstract »    Full Text »    PDF »
Hedgehog: functions and mechanisms.
M. Varjosalo and J. Taipale (2008)
Genes & Dev. 22, 2454-2472
   Abstract »    Full Text »    PDF »
Hedgehog signalling in endocrine development and disease.
P. J King, L. Guasti, and E. Laufer (2008)
J. Endocrinol. 198, 439-450
   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