Gene Symbol: Smo
Description: smoothened, frizzled class receptor
Alias: E130215L21Rik, Smoh, bnb, smoothened, smoothened homolog, bent body
Species: mouse
Products:     Smo

Top Publications

  1. Kim J, Kato M, Beachy P. Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc Natl Acad Sci U S A. 2009;106:21666-71 pubmed publisher
    ..Hh) protein signal has been shown to alter ciliary localization of the mammalian Hh receptor components Smoothened (Smo) and Patched (Ptc), and mutations that disrupt the structure and function of the cilium also disrupt Hh-..
  2. Kasarskis A, Manova K, Anderson K. A phenotype-based screen for embryonic lethal mutations in the mouse. Proc Natl Acad Sci U S A. 1998;95:7485-90 pubmed
    ..Two mutations produce novel early phenotypes and map to regions of the genome not previously implicated in embryonic patterning. ..
  3. Lin L, Bu L, Cai C, Zhang X, Evans S. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Dev Biol. 2006;295:756-63 pubmed
    ..Shh signals through the unique activating receptor smoothened (Smo). To investigate the role of hedgehog signaling in the isl1 domain, we ablated smo utilizing isl1-cre...
  4. Wang Y, Zhou Z, Walsh C, McMahon A. Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation. Proc Natl Acad Sci U S A. 2009;106:2623-8 pubmed publisher
    b>Smoothened (Smo), a 7-pass transmembrane protein, is essential for transduction of a Hedgehog (Hh) signal across the cell membrane...
  5. Cheung H, Zhang X, Ribeiro A, Mo R, Makino S, Puviindran V, et al. The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling. Sci Signal. 2009;2:ra29 pubmed publisher
    ..Thus, Kif7 is a missing component of the mammalian Hh signaling machinery, implying a greater commonality between the Drosophila and mammalian system than the prevailing view suggests. ..
  6. Liem K, He M, Ocbina P, Anderson K. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc Natl Acad Sci U S A. 2009;106:13377-82 pubmed publisher
    ..of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factors...
  7. Chen M, Wilson C, Li Y, Law K, Lu C, Gacayan R, et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 2009;23:1910-28 pubmed publisher
    ..In contrast, fly Smo is unable to translocate to the primary cilium and activate the mammalian Hh pathway...
  8. Xu Q, Guo L, Moore H, Waclaw R, Campbell K, Anderson S. Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron. 2010;65:328-40 pubmed publisher
    ..In this paper, we report that mosaic elimination in the medial ganglionic eminence (MGE) of Smo, a key effector of SHH signaling, reveals that MGE progenitors retain a remarkable degree of plasticity during the ..
  9. Gritli Linde A, Bei M, Maas R, Zhang X, Linde A, McMahon A. Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development. 2002;129:5323-37 pubmed
    ..and extend our understanding of Shh's actions in odontogenesis, we have used the Cre-loxP system to remove Smoothened (Smo) activity in the dental epithelium...

More Information


  1. Chen Y, Sasai N, Ma G, Yue T, Jia J, Briscoe J, et al. Sonic Hedgehog dependent phosphorylation by CK1? and GRK2 is required for ciliary accumulation and activation of smoothened. PLoS Biol. 2011;9:e1001083 pubmed publisher
    ..Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo), but how vertebrate Smo is activated remains poorly understood...
  2. Larkins C, Aviles G, East M, Kahn R, Caspary T. Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins. Mol Biol Cell. 2011;22:4694-703 pubmed publisher
    ..Significantly, we found Smoothened (Smo) is enriched in Arl13b-null cilia regardless of Shh pathway stimulation, indicating Arl13b regulates the ..
  3. Jeong J, Mao J, Tenzen T, Kottmann A, McMahon A. Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. Genes Dev. 2004;18:937-51 pubmed
    ..Further, our analysis of Shh-Fox gene regulatory interactions leads us to propose that Fox genes mediate the action of Shh in facial development. ..
  4. Liem K, Ashe A, He M, Satir P, Moran J, Beier D, et al. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. J Cell Biol. 2012;197:789-800 pubmed publisher
    ..In contrast, the membrane proteins Arl13b, ACIII, and Smo failed to localize to primary cilia in the absence of IFT-A...
  5. Corbit K, Aanstad P, Singla V, Norman A, Stainier D, Reiter J. Vertebrate Smoothened functions at the primary cilium. Nature. 2005;437:1018-21 pubmed
    ..Here we show that mammalian Smoothened (Smo), a seven-transmembrane protein essential for Hh signalling, is expressed on the primary cilium...
  6. Stone D, Hynes M, Armanini M, Swanson T, Gu Q, Johnson R, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384:129-34 pubmed
    ..We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly...
  7. Hu M, Mo R, Bhella S, Wilson C, Chuang P, Hui C, et al. GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development. 2006;133:569-78 pubmed
    Truncating mutations in Gli3, an intracellular effector in the SHH-SMO-GLI signaling pathway, cause renal aplasia/dysplasia in humans and mice. Yet, the pathogenic mechanisms are undefined...
  8. Wilson C, Chen M, Chuang P. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS ONE. 2009;4:e5182 pubmed publisher
    Activation of Hedgehog (Hh) signaling requires the transmembrane protein Smoothened (Smo), a member of the G-protein coupled receptor superfamily...
  9. Kovacs J, Whalen E, Liu R, Xiao K, Kim J, Chen M, et al. Beta-arrestin-mediated localization of smoothened to the primary cilium. Science. 2008;320:1777-81 pubmed publisher
    beta-Arrestins have important roles in the regulation of seven-transmembrane receptors (7TMRs). Smoothened (Smo) is a 7TMR that mediates effects of Hedgehog on developmental processes and whose dysregulation may cause tumorigenesis...
  10. Blaess S, Corrales J, Joyner A. Sonic hedgehog regulates Gli activator and repressor functions with spatial and temporal precision in the mid/hindbrain region. Development. 2006;133:1799-809 pubmed
    ..Thus, the precise spatial and temporal regulation of Gli2A and Gli3R by Shh is instrumental in coordinating mid/hindbrain development in three dimensions. ..
  11. Lavine K, Long F, Choi K, Smith C, Ornitz D. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development. 2008;135:3161-71 pubmed publisher
    ..Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages. ..
  12. White A, Lavine K, Ornitz D. FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network. Development. 2007;134:3743-52 pubmed
    ..These data suggest a molecular mechanism through which FGF9 and SHH signaling coordinately control the growth and patterning of the lung capillary plexus, and regulate the temporal and spatial expression of Vegfa. ..
  13. Tran P, Haycraft C, Besschetnova T, Turbe Doan A, Stottmann R, Herron B, et al. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008;40:403-410 pubmed publisher
    ..In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia...
  14. Ocbina P, Anderson K. Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev Dyn. 2008;237:2030-8 pubmed publisher
    ..Exposure to Sonic hedgehog (Shh) ligand or expression of an activated allele of Smo, SmoA1, activates an Hh reporter in wild-type MEFs, but not in MEFs derived from embryos that lack IFT172 or the ..
  15. Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales S, et al. The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling. Cell. 2013;152:210-23 pubmed publisher
    ..Conversely, Shh signaling directs Gpr161 to be internalized from cilia, preventing its activity. Thus, Gpr161 defines a morphogenetic pathway coupling protein kinase A activation to Shh signaling during neural tube development. ..
  16. Dorn K, Hughes C, Rohatgi R. A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev Cell. 2012;23:823-35 pubmed publisher
    Vertebrate Hedgehog (Hh) signaling is initiated at primary cilia by the ligand-triggered accumulation of Smoothened (Smo) in the ciliary membrane. The underlying biochemical mechanisms remain unknown...
  17. Mahjoub M, Stearns T. Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling. Curr Biol. 2012;22:1628-34 pubmed publisher
    ..found that cells with extra centrioles often formed more than one cilium, had reduced ciliary concentration of Smoothened in response to Sonic hedgehog stimulation, and reduced Shh pathway transcriptional activation...
  18. Nehmé R, Joubert O, Bidet M, Lacombe B, Polidori A, Pucci B, et al. Stability study of the human G-protein coupled receptor, Smoothened. Biochim Biophys Acta. 2010;1798:1100-10 pubmed publisher
    b>Smoothened is a member of the G-protein coupled receptor (GPCR) family responsible for the transduction of the Hedgehog signal to the intracellular effectors of the Hedgehog signaling pathway...
  19. Wijgerde M, McMahon J, Rule M, McMahon A. A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev. 2002;16:2849-64 pubmed
    ..b>Smoothened (Smo) is essential for all Hedgehog (Hh) signaling, and genetic inactivation of Smo cells autonomously blocks ..
  20. Huangfu D, Anderson K. Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci U S A. 2005;102:11325-30 pubmed
    ..The phenotypes of the IFT mutants, however, are not identical to mutants that lack Smoothened (Smo), an essential activator of the Hh pathway...
  21. Caspary T, García García M, Huangfu D, Eggenschwiler J, Wyler M, Rakeman A, et al. Mouse Dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling. Curr Biol. 2002;12:1628-32 pubmed
    ..We positionally cloned the genes responsible for two of the mutant phenotypes, smoothened and dispatched, which are homologs of Drosophila Hh pathway components...
  22. Varjosalo M, Li S, Taipale J. Divergence of hedgehog signal transduction mechanism between Drosophila and mammals. Dev Cell. 2006;10:177-86 pubmed
    ..In Drosophila, the kinesin-like protein Costal2 (Cos2), which associates directly with the Hh receptor component Smoothened (Smo), is essential for suppression of the transcriptional activity of Ci in the absence of ligand...
  23. Machold R, Hayashi S, Rutlin M, Muzumdar M, Nery S, Corbin J, et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron. 2003;39:937-50 pubmed
    ..the telencephalon from early neurogenesis, we examined conditional null alleles of both the Sonic hedgehog and Smoothened genes...
  24. Milenkovic L, Scott M, Rohatgi R. Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium. J Cell Biol. 2009;187:365-74 pubmed publisher
    ..A major challenge in the field is to understand protein trafficking to cilia. The Hedgehog (Hh) pathway protein Smoothened (Smo), a 7-pass transmembrane protein, moves to cilia when a ligand is received...
  25. Eggenschwiler J, Bulgakov O, Qin J, Li T, Anderson K. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Dev Biol. 2006;290:1-12 pubmed
    ..Although the membrane proteins Patched and Smoothened change subcellular localization in response to Shh, double mutant analysis demonstrates that Rab23 does not work ..
  26. Corrales J, Blaess S, Mahoney E, Joyner A. The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development. 2006;133:1811-21 pubmed
    ..By progressively lowering signaling by removing Gli1 and Gli2 or the Shh receptor smoothened, we found the extent of foliation is gradually reduced, and that this correlates with a decrease in the duration ..
  27. Law K, Makino S, Mo R, Zhang X, Puviindran V, Hui C. Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular Gli activities in Hedgehog signaling. PLoS ONE. 2012;7:e50193 pubmed publisher
  28. Wall D, Mears A, McNeill B, Mazerolle C, Thurig S, Wang Y, et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol. 2009;184:101-12 pubmed publisher
    ..This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior. ..
  29. Patterson V, Damrau C, Paudyal A, Reeve B, Grimes D, Stewart M, et al. 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. Hum Mol Genet. 2009;18:1719-39 pubmed publisher
    ..We demonstrate that Tulp3 acts genetically downstream of Shh and Smoothened (Smo) in neural tube patterning and exhibits a genetic interaction with Gli3 in limb development...
  30. Riobo N, Saucy B, DiLizio C, Manning D. Activation of heterotrimeric G proteins by Smoothened. Proc Natl Acad Sci U S A. 2006;103:12607-12 pubmed
    The mechanisms by which the activation of Smoothened (Smo), a protein essential to the actions of the Hedgehog family of secreted proteins, is translated into signals that converge on the Gli transcription factors are not fully understood...
  31. Yang H, Xiang J, Wang N, Zhao Y, Hyman J, Li S, et al. Converse conformational control of smoothened activity by structurally related small molecules. J Biol Chem. 2009;284:20876-84 pubmed publisher
    The seven-pass transmembrane protein Smoothened (Smo) is an essential component of the Hedgehog (Hh) signaling pathway that is critically involved in normal animal development as well as pathological malignancies...
  32. Meloni A, Fralish G, Kelly P, Salahpour A, Chen J, Wechsler Reya R, et al. Smoothened signal transduction is promoted by G protein-coupled receptor kinase 2. Mol Cell Biol. 2006;26:7550-60 pubmed
    ..In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli...
  33. Szczepny A, Hime G, Loveland K. Expression of hedgehog signalling components in adult mouse testis. Dev Dyn. 2006;235:3063-70 pubmed
    ..The mRNAs encoding key effectors of Hh signalling, Ptc2, Smo, and Fu, are also most apparent in spermatogonia, spermatocytes, and to a lower extent in round spermatids...
  34. Keady B, Samtani R, Tobita K, Tsuchya M, San Agustin J, Follit J, et al. IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport. Dev Cell. 2012;22:940-51 pubmed publisher
    ..IFT25 have defects in the signal-dependent transport of multiple Hedgehog components including Patched-1, Smoothened, and Gli2, and fail to activate the pathway upon stimulation...
  35. Rohatgi R, Milenkovic L, Scott M. Patched1 regulates hedgehog signaling at the primary cilium. Science. 2007;317:372-6 pubmed
    ..Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia...
  36. Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell. 2001;106:781-92 pubmed
    Genetic analyses in Drosophila have demonstrated that the multipass membrane protein Smoothened (Smo) is essential for all Hedgehog signaling...
  37. St Jacques B, Dassule H, Karavanova I, Botchkarev V, Li J, Danielian P, et al. Sonic hedgehog signaling is essential for hair development. Curr Biol. 1998;8:1058-68 pubmed
    ..Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle. ..
  38. Tuson M, He M, Anderson K. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube. Development. 2011;138:4921-30 pubmed publisher
    ..The data show that PKA does not affect cilia length or trafficking of smoothened (Smo) in the cilium...
  39. Boehlke C, Bashkurov M, Buescher A, Krick T, John A, Nitschke R, et al. Differential role of Rab proteins in ciliary trafficking: Rab23 regulates smoothened levels. J Cell Sci. 2010;123:1460-7 pubmed publisher
    ..compared the effect of Rab8, Rab5 and Rab23 on the ciliary transport of the HH-associated transmembrane receptor Smoothened, the microtubular tip protein EB1, and the receptor protein Kim1...
  40. Zhao Y, Tong C, Jiang J. Hedgehog regulates smoothened activity by inducing a conformational switch. Nature. 2007;450:252-8 pubmed
    Hedgehog (HH) morphogen is essential for metazoan development. The seven-transmembrane protein smoothened (SMO) transduces the HH signal across the plasma membrane, but how SMO is activated remains poorly understood...
  41. May S, Ashique A, Karlen M, Wang B, Shen Y, Zarbalis K, et al. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol. 2005;287:378-89 pubmed
    ..The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity...
  42. Balordi F, Fishell G. Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci. 2007;27:5936-47 pubmed
    ..These results suggest that Hedgehog signaling is required for the maintenance of the B and C cell populations and indirectly for the migration of the neurons that are generated from the adult stem cell niche. ..
  43. Chamberlain C, Jeong J, Guo C, Allen B, McMahon A. Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning. Development. 2008;135:1097-106 pubmed publisher
    ..This study, in which we directly observe, measure, localize and modify notochord-derived Shh ligand in the context of neural patterning, provides several new insights into mechanisms of Shh morphogen action...
  44. Hu Q, Milenkovic L, Jin H, Scott M, Nachury M, Spiliotis E, et al. A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science. 2010;329:436-9 pubmed publisher
    ..Thus, SEPT2 is part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium. ..
  45. Ocbina P, Eggenschwiler J, Moskowitz I, Anderson K. Complex interactions between genes controlling trafficking in primary cilia. Nat Genet. 2011;43:547-53 pubmed publisher
  46. Charron F, Stein E, Jeong J, McMahon A, Tessier Lavigne M. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 2003;113:11-23 pubmed
    ..Cyclopamine-mediated inhibition of the Shh signaling mediator Smoothened (Smo) or conditional inactivation of Smo in commissural neurons indicate that Smo activity is important for the ..
  47. Fuccillo M, Rallu M, McMahon A, Fishell G. Temporal requirement for hedgehog signaling in ventral telencephalic patterning. Development. 2004;131:5031-40 pubmed
    ..brain by embryonic day 9 of development, using a FoxG1(Cre) driver line to mediate the removal of a conditional smoothened null allele...
  48. Hoffmann A, Peterson M, Friedland Little J, Anderson S, Moskowitz I. sonic hedgehog is required in pulmonary endoderm for atrial septation. Development. 2009;136:1761-70 pubmed publisher
    ..These data suggest a model in which respiratory endoderm patterns the morphogenesis of cardiac structural components required for efficient cardiopulmonary circulation. ..
  49. Rohatgi R, Milenkovic L, Corcoran R, Scott M. Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc Natl Acad Sci U S A. 2009;106:3196-201 pubmed publisher
    ..Damage to Hh transduction machinery can lead to birth defects and cancer. The transmembrane protein Smoothened (Smo) relays the Hh signal and is an important drug target in cancer...
  50. Long F, Zhang X, Karp S, Yang Y, McMahon A. Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development. 2001;128:5099-108 pubmed
    ..b>Smoothened (Smo) is a transmembrane protein that transduces all Hh signals...
  51. Long F, Chung U, Ohba S, McMahon J, Kronenberg H, McMahon A. Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development. 2004;131:1309-18 pubmed determine whether Ihh is directly required for osteoblast differentiation, we have genetically manipulated smoothened (Smo), which encodes a transmembrane protein that is essential for transducing all Hedgehog (Hh) signals...
  52. Manuel M, Martynoga B, Yu T, West J, Mason J, Price D. The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice. Development. 2010;137:487-97 pubmed publisher
    ..These findings indicate that, in addition to regulating the production of ventralising signals, Foxg1 acts cell-autonomously in the telencephalon to ensure that cells develop the competence to adopt ventral identities. ..
  53. Luchetti G, Sircar R, Kong J, Nachtergaele S, Sagner A, Byrne E, et al. Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling. elife. 2016;5: pubmed publisher
    ..Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals...