Genomes and Genes
Gene Symbol: smo
Description: smoothened, frizzled class receptor
Alias: CHUNP6862, smoh, smu, wu:fb70b01, wu:fc39h03, smoothened homolog, slow muscle omitted
- Woods I, Talbot W. The you gene encodes an EGF-CUB protein essential for Hedgehog signaling in zebrafish. PLoS Biol. 2005;3:e66 pubmed..Our positional cloning and functional studies demonstrate that You is a novel extracellular component of the Hedgehog pathway in vertebrates. ..
- 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...
- Wada N, Javidan Y, Nelson S, Carney T, Kelsh R, Schilling T. Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull. Development. 2005;132:3977-88 pubmed
- Chen W, Burgess S, Hopkins N. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development. 2001;128:2385-96 pubmed..Taken together, these data demonstrate the conserved role of vertebrate smoothened in the hedgehog signaling pathway, and reveal similarities and differences of hedgehog function between teleosts and amniotes. ..
- Winata C, Korzh S, Kondrychyn I, Zheng W, Korzh V, Gong Z. Development of zebrafish swimbladder: The requirement of Hedgehog signaling in specification and organization of the three tissue layers. Dev Biol. 2009;331:222-36 pubmed publisher..Furthermore, time-specific Hh inhibition by cyclopamine revealed different requirements of Hh signaling in the formation and organization of all three tissue layers of swimbladder...
- Shitasako S, Ito Y, Ito R, Ueda Y, Shimizu Y, Ohshima T. Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish. Dev Neurobiol. 2017;77:1206-1220 pubmed publisher..Our experimental data also indicate the involvement of these signaling pathways in neural differentiation from NSCs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1206-1220, 2017. ..
- Varshney G, Huang H, Zhang S, Lu J, Gildea D, Yang Z, et al. The Zebrafish Insertion Collection (ZInC): a web based, searchable collection of zebrafish mutations generated by DNA insertion. Nucleic Acids Res. 2013;41:D861-4 pubmed publisher..In the future, ZInC may include data from other insertional mutation projects as well. ZInC cross-references all integration data with the ZFIN (http://zfin.org/). ..
- Stacher Hörndli C, Chien C. Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk. Development. 2012;139:2604-13 pubmed publisher..Together, our results support a model in which Shh acts in RGC axon pathfinding indirectly by regulating axon guidance cues at the optic disc through patterning of the optic stalk. ..
- Hirsinger E, Stellabotte F, Devoto S, Westerfield M. Hedgehog signaling is required for commitment but not initial induction of slow muscle precursors. Dev Biol. 2004;275:143-57 pubmed
- Pendeville H, Winandy M, Manfroid I, Nivelles O, Motte P, Pasque V, et al. Zebrafish Sox7 and Sox18 function together to control arterial-venous identity. Dev Biol. 2008;317:405-16 pubmed publisher..The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest that Sox7 and Sox18 control arterial-venous identity by regulating Gridlock expression. ..
- Thomas N, Koudijs M, van Eeden F, Joyner A, Yelon D. Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential. Development. 2008;135:3789-99 pubmed publisher..Thus, Hh signaling plays an essential early role in defining the optimal number of cardiomyocytes, making it an attractive target for manipulation of multipotent progenitor cells. ..
- Wong K, Rehn K, Palencia Desai S, Kohli V, Hunter W, Uhl J, et al. Hedgehog signaling is required for differentiation of endocardial progenitors in zebrafish. Dev Biol. 2012;361:377-91 pubmed publisher..Simultaneous knockdown of the two zebrafish sonic hedgehog homologs, shh and twhh or Hh co-receptor smoothened (smo) resulted in similar defects in endocardial morphogenesis...
- Teraoka H, Russell C, Regan J, Chandrasekhar A, Concha M, Yokoyama R, et al. Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos. J Neurobiol. 2004;60:275-88 pubmed..Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class. ..
- Teraoka H, Dong W, Okuhara Y, Iwasa H, Shindo A, Hill A, et al. Impairment of lower jaw growth in developing zebrafish exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and reduced hedgehog expression. Aquat Toxicol. 2006;78:103-13 pubmed..TCDD may impair jaw growth through other pathway(s) in addition to Hh signaling. ..
- 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 publisherThe 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...
- Sanek N, Taylor A, Nyholm M, Grinblat Y. Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated gene expression. Development. 2009;136:3791-800 pubmed publisher..These data uncover a novel, essential role for Zic2a as a modulator of Hh-activated gene expression in the developing forebrain and advance our understanding of a key gene regulatory network that, when disrupted, causes HPE. ..
- Rohr K, Barth K, Varga Z, Wilson S. The nodal pathway acts upstream of hedgehog signaling to specify ventral telencephalic identity. Neuron. 2001;29:341-51 pubmed..Thus, the Nodal pathway regulates ventral forebrain patterning through both Hedgehog signaling-dependent and -independent mechanisms. ..
- David N, Sapede D, Saint Etienne L, Thisse C, Thisse B, Dambly Chaudiere C, et al. Molecular basis of cell migration in the fish lateral line: role of the chemokine receptor CXCR4 and of its ligand, SDF1. Proc Natl Acad Sci U S A. 2002;99:16297-302 pubmed..We conclude that both the formation and the innervation of this system depend on the SDF1-CXCR4 system, which has also been implicated in several migration events in humans, including metastasis formation and lymphocyte homing. ..
- Feng X, Adiarte E, Devoto S. Hedgehog acts directly on the zebrafish dermomyotome to promote myogenic differentiation. Dev Biol. 2006;300:736-46 pubmed..We propose that Hedgehog signaling acts at multiple times on different lineages, through different downstream pathways, to promote myogenic differentiation. ..
- Tallafuss A, Adolf B, Bally Cuif L. Selective control of neuronal cluster size at the forebrain/midbrain boundary by signaling from the prechordal plate. Dev Dyn. 2003;227:524-35 pubmed..1/no-isthmus and smoothened/slow muscle omitted mutants, where identities adjacent to the six3 cluster are altered; however, in these mutants, the ..
- Hadzhiev Y, Lele Z, Schindler S, Wilson S, Ahlberg P, Strahle U, et al. Hedgehog signaling patterns the outgrowth of unpaired skeletal appendages in zebrafish. BMC Dev Biol. 2007;7:75 pubmed..The median fins evolved before paired fins in early craniates, thus the patterning of the median fins may be an ancestral mechanism that controls the outgrowth of skeletogenic appendages in vertebrates. ..
- Barresi M, Burton S, Dipietrantonio K, Amsterdam A, Hopkins N, Karlstrom R. Essential genes for astroglial development and axon pathfinding during zebrafish embryogenesis. Dev Dyn. 2010;239:2603-18 pubmed publisher..The genes disrupted in these viral lines have all been identified, providing a powerful new resource for the study of axon guidance, glio- and neurogenesis, and neuron-glial interactions during development of the vertebrate CNS. ..
- Tehrani Z, Lin S. Antagonistic interactions of hedgehog, Bmp and retinoic acid signals control zebrafish endocrine pancreas development. Development. 2011;138:631-40 pubmed publisher..We show that RA downregulates the Hh signaling components ptc1 and smo in endodermal explants, indicating a possible molecular mechanism for blocking axial mesoderm-derived Hh ligands ..
- Cheesman S, Eisen J. gsh1 demarcates hypothalamus and intermediate spinal cord in zebrafish. Gene Expr Patterns. 2004;5:107-12 pubmed..These data suggest gsh1 may play a role in patterning cell types generated in these domains. ..
- Dutta S, Dietrich J, Aspöck G, Burdine R, Schier A, Westerfield M, et al. pitx3 defines an equivalence domain for lens and anterior pituitary placode. Development. 2005;132:1579-90 pubmed..During mid-somitogenesis, Hedgehog then acts on the established median placode as a necessary and sufficient signal to specify pituitary cell types. ..
- McFarland K, Topczewska J, Weidinger G, Dorsky R, Appel B. Hh and Wnt signaling regulate formation of olig2+ neurons in the zebrafish cerebellum. Dev Biol. 2008;318:162-71 pubmed publisher..Specifically, we propose that Hedgehog limits the range of Wnt signaling, which is necessary for olig2(+) neuron development. ..
- Ke Z, Kondrichin I, Gong Z, Korzh V. Combined activity of the two Gli2 genes of zebrafish play a major role in Hedgehog signaling during zebrafish neurodevelopment. Mol Cell Neurosci. 2008;37:388-401 pubmed..Gli2b acts in cell proliferation and plays an early role in the hindbrain within a regulatory cascade involving Notch and Ngn1, as well as a role as specific activator in rhombomere 4. ..
- Parkin C, Allen C, Ingham P. Hedgehog signalling is required for cloacal development in the zebrafish embryo. Int J Dev Biol. 2009;53:45-57 pubmed publisher..These studies establish the zebrafish as a model for ARMs, and for the elucidation of other pathways involved in hindgut developmental processes. ..
- McCabe J, Leahy D. Smoothened goes molecular: new pieces in the hedgehog signaling puzzle. J Biol Chem. 2015;290:3500-7 pubmed publisher..Hh and Patched (Ptc), a 12-pass integral membrane protein, lead to modulation of the function of Smoothened (Smo), a 7-pass integral membrane protein, has defied standard biochemical characterization...
- Albert S, Muller F, Fischer N, Biellmann D, Neumann C, Blader P, et al. Cyclops-independent floor plate differentiation in zebrafish embryos. Dev Dyn. 2003;226:59-66 pubmed..This finding suggests that the correct temporal development of the MFP is required for the distinction of LFP and MFP cells in wild-type embryos. ..
- Lien H, Yuan R, Chou C, Chen Y, Hung C, Hu C, et al. Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2?. Sci Rep. 2016;6:28297 pubmed publisher..Overexpression of cyclin Dx mRNA in Hif2? morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons. ..
- Paulus J, Willer G, Willer J, Gregg R, Halloran M. Muscle contractions guide rohon-beard peripheral sensory axons. J Neurosci. 2009;29:13190-201 pubmed publisher..This work suggests that the mechanical forces generated by muscle contractions are necessary for proper sensory axon pathfinding in vivo. ..
- Ju B, Spitsbergen J, Eden C, Taylor M, Chen W. Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol Cancer. 2009;8:40 pubmed publisher..These results suggest that co-activation of the hedgehog and AKT pathways promote tumorigenesis, and that the binary transgenic approach is a useful tool for studying interaction of oncogenes and oncogenic pathways in zebrafish. ..
- Williams C, Hempel J, Hao J, Frist A, Williams M, Fleming J, et al. An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition. Cell Rep. 2015;11:43-50 pubmed publisher..While a variety of small molecules target Smoothened (Smo) as a strategy for Hh inhibition, Smo gain-of-function mutations have limited their clinical implementation...
- Eberhart J, Swartz M, Crump J, Kimmel C. Early Hedgehog signaling from neural to oral epithelium organizes anterior craniofacial development. Development. 2006;133:1069-77 pubmed..We observe that in mutants for the Hh co-receptor smoothened (smo) the condensation of this specific subset of crest cells fails, and expression of several genes is lost in the ..
- Wan H, Korzh S, Li Z, Mudumana S, Korzh V, Jiang Y, et al. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter. Exp Cell Res. 2006;312:1526-39 pubmed..By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is ..
- Hollway G, Maule J, Gautier P, Evans T, Keenan D, Lohs C, et al. Scube2 mediates Hedgehog signalling in the zebrafish embryo. Dev Biol. 2006;294:104-18 pubmed..Epistatic and molecular analyses position Scube2 function upstream of Smoothened (Smoh), the signalling component of the HH receptor complex, suggesting that Scube2 may act during HH signal transduction ..
- Mavropoulos A, Devos N, Biemar F, Zecchin E, Argenton F, Edlund H, et al. sox4b is a key player of pancreatic alpha cell differentiation in zebrafish. Dev Biol. 2005;285:211-23 pubmed..Taken together, these data demonstrate that, in zebrafish, sox4b is expressed transiently during endocrine cell differentiation and plays a crucial role in the generation of alpha endocrine cells. ..
- Zhao Z, Lee R, Pusapati G, Iyu A, Rohatgi R, Ingham P. An essential role for Grk2 in Hedgehog signalling downstream of Smoothened. EMBO Rep. 2016;17:739-52 pubmed publisher..Zebrafish embryos lacking all Grk2 activity are refractory to both Sonic hedgehog (Shh) and oncogenic Smoothened (Smo) activity, but remain responsive to inhibition of cAMP-dependent protein kinase (PKA) activity...
- Yee N, Zhou W, Liang I. Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer. Dis Model Mech. 2011;4:240-54 pubmed publisher..Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg(2+)-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis. ..
- Zeng L, Carter A, Childs S. miR-145 directs intestinal maturation in zebrafish. Proc Natl Acad Sci U S A. 2009;106:17793-8 pubmed publisher..miR-145 therefore plays a critical role in promoting the maturation of both layers of the gut during development through regulation of gata6. ..
- Hammond K, Loynes H, Folarin A, Smith J, Whitfield T. Hedgehog signalling is required for correct anteroposterior patterning of the zebrafish otic vesicle. Development. 2003;130:1403-17 pubmed..We demonstrate that two strong Hedgehog pathway mutants, chameleon (con(tf18b)) and slow muscle omitted (smu(b641)) exhibit a striking partial mirror image duplication of anterior otic structures, concomitant ..
- Evron T, Philipp M, Lu J, Meloni A, Burkhalter M, Chen W, et al. Growth Arrest Specific 8 (Gas8) and G protein-coupled receptor kinase 2 (GRK2) cooperate in the control of Smoothened signaling. J Biol Chem. 2011;286:27676-86 pubmed publisherThe G protein-coupled receptor (GPCR)-like molecule Smoothened (Smo) undergoes dynamic intracellular trafficking modulated by the microtubule associated kinase GRK2 and recruitment of ?-arrestin...
- White R, Collins J, Sealy I, Wali N, Dooley C, Digby Z, et al. A high-resolution mRNA expression time course of embryonic development in zebrafish. elife. 2017;6: pubmed publisher..To make this dataset a useful baseline reference, the data can be browsed and downloaded at Expression Atlas and Ensembl. ..
- Ju B, Chen W, Spitsbergen J, Lu J, Vogel P, Peters J, et al. Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway. Oncogenesis. 2014;3:e96 pubmed publisher..In conclusion, we demonstrate that activated Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first OPG model not associated with neurofibromatosis 1. ..
- Nachtergaele S, Whalen D, Mydock L, Zhao Z, Malinauskas T, Krishnan K, et al. Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling. elife. 2013;2:e01340 pubmed publisherThe Hedgehog (Hh) signal is transduced across the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present the 2...
- Williams C, Kim S, Ni T, Mitchell L, Ro H, Penn J, et al. Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate. Dev Biol. 2010;341:196-204 pubmed publisher..endothelial progenitor cells) during arterial-venous specification utilizing zebrafish mutations in Smoothened (Smo), a G protein-coupled receptor essential for Hh signaling...
- Masai I, Yamaguchi M, Tonou Fujimori N, Komori A, Okamoto H. The hedgehog-PKA pathway regulates two distinct steps of the differentiation of retinal ganglion cells: the cell-cycle exit of retinoblasts and their neuronal maturation. Development. 2005;132:1539-53 pubmed..This dual requirement of Hh signalling in RGC differentiation implies that the regulation of a neurogenic wave is more complex in the zebrafish retina than in the Drosophila eye. ..
- diIorio P, Moss J, Sbrogna J, Karlstrom R, Moss L. Sonic hedgehog is required early in pancreatic islet development. Dev Biol. 2002;244:75-84 pubmed..The early action of Shh may be part of a more general process allowing neuroendocrine cells to originate in nonneuroectodermally derived tissues. ..
- Han Y, Xiong Y, Shi X, Wu J, Zhao Y, Jiang J. Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-?2 nuclear import system. PLoS Biol. 2017;15:e2002063 pubmed publisher..Our study unravels the molecular mechanism and cellular machinery regulating Gli ciliary localization and identifies Kap?2 as a critical regulator of the Hh pathway and a potential drug target for Hh-driven cancers. ..
- Lee R, Ng A, Ingham P. Ribozyme Mediated gRNA Generation for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis. PLoS ONE. 2016;11:e0166020 pubmed publisher..Our method provides a streamlined approach to test gRNA efficiency as well as increasing the versatility of conditional gene knock out in zebrafish. ..
- Alvers A, Ryan S, Scherz P, Huisken J, Bagnat M. Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling. Development. 2014;141:1110-9 pubmed publisher..We show that lumen resolution, but not lumen opening, is impaired in smoothened (smo) mutants, indicating that fluid-driven lumen enlargement and resolution are two distinct processes...
- Schebesta M, Serluca F. olig1 Expression identifies developing oligodendrocytes in zebrafish and requires hedgehog and notch signaling. Dev Dyn. 2009;238:887-98 pubmed publisher..Lastly, knockdown of Olig1 in an Olig2-sensitized background did result in defects in CNS myelination, indicating a functional overlap between Olig1 and Olig2 proteins. ..
- Philipp M, Fralish G, Meloni A, Chen W, MacInnes A, BARAK L, et al. Smoothened signaling in vertebrates is facilitated by a G protein-coupled receptor kinase. Mol Biol Cell. 2008;19:5478-89 pubmed publisher..Together, these data suggest that a GRK functions as a vertebrate kinase for Smoothened, promoting Hedgehog signal transduction during early development. ..
- Ochi H, Pearson B, Chuang P, Hammerschmidt M, Westerfield M. Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened. Dev Biol. 2006;297:127-40 pubmed..These data support a model in which Hhip regulates muscle development both by sequestering Hedgehog and by modulating localization of Smoothened. ..
- Nicolson T. The genetics of hearing and balance in zebrafish. Annu Rev Genet. 2005;39:9-22 pubmed..This review addresses the most recent advances in our understanding of how the ear forms and discusses the molecules in hair cells that are essential for sensing sound and movement in the zebrafish. ..
- Kay J, Link B, Baier H. Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina. Development. 2005;132:2573-85 pubmed
- Take uchi M, Clarke J, Wilson S. Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity. Development. 2003;130:955-68 pubmed..Taking all these results together, we present a model of the partitioning of the optic vesicle along its proximo-distal axis. ..
- Wilson C, Nguyen C, Chen M, Yang J, Gacayan R, Huang J, et al. Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. Nature. 2009;459:98-102 pubmed publisher..Our results delineate a new pathway for central pair apparatus assembly, identify common regulators of Hh signalling and motile ciliogenesis, and provide insights into the evolution of the Hh cascade. ..
- Culverwell J, Karlstrom R. Making the connection: retinal axon guidance in the zebrafish. Semin Cell Dev Biol. 2002;13:497-506 pubmed..The combination of zebrafish genetic and embryological approaches promises to greatly increase our understanding of how multiple guidance mechanisms establish the complex neural interconnectivity of the vertebrate brain. ..
- Esain V, Postlethwait J, Charnay P, Ghislain J. FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9. Development. 2010;137:33-42 pubmed publisher..Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity. ..
- Wang X, Zhao Z, Müller J, Iyu A, Khng A, Guccione E, et al. Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish. Biol Open. 2013;2:1203-13 pubmed publisher..Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a. ..
- Cooper T, Spitsbergen J. Valvular and Mural Endocardiosis in Aging Zebrafish (Danio rerio). Vet Pathol. 2016;53:504-9 pubmed publisher..Valvular endocardiosis is a significant age- and husbandry-related background finding in zebrafish and should be considered in the design and interpretation of research studies. ..
- Anderson N, Li D, Peng H, Laroche F, Mansour M, Gjini E, et al. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia. 2016;30:1365-74 pubmed publisher..Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy. ..
- Mich J, Chen J. Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish. Development. 2011;138:5113-9 pubmed publisher..We also provide evidence that RA pathway activation can modulate Gli function in a Hh ligand-independent manner. These findings support a model in which Hh and RA signaling cooperate to promote PMN cell fates in zebrafish. ..