Gene Symbol: Ihh
Description: Indian hedgehog
Alias: HHG-2, indian hedgehog protein
Species: mouse
Products:     Ihh

Top Publications

  1. Ochiai T, Shibukawa Y, Nagayama M, Mundy C, Yasuda T, Okabe T, et al. Indian hedgehog roles in post-natal TMJ development and organization. J Dent Res. 2010;89:349-54 pubmed publisher
    Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation...
  2. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng J, Behringer R, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17-29 pubmed
    ..Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells. ..
  3. Jensen A, Wallace V. Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina. Development. 1997;124:363-71 pubmed
    ..These findings suggest that hedgehog and patched are part of a conserved signalling pathway in retinal development in mammals and insects. ..
  4. Liu Y, Liu C, Yamada Y, Fan C. Growth arrest specific gene 1 acts as a region-specific mediator of the Fgf10/Fgf8 regulatory loop in the limb. Development. 2002;129:5289-300 pubmed
    ..Our data provide evidence that Gas1 acts to maintain high levels of FGF10 at the tip mesenchyme and support the proposal that Fgf10 expression in this region is crucial for maintaining Fgf8 expression in the AER. ..
  5. Akiyama H, Lyons J, Mori Akiyama Y, Yang X, Zhang R, Zhang Z, et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004;18:1072-87 pubmed
    ..Our results strongly suggest that chondrogenesis is controlled by interactions between Sox9 and the Wnt/beta-catenin signaling pathway. ..
  6. Tsumaki N, Tanaka K, Arikawa Hirasawa E, Nakase T, Kimura T, Thomas J, et al. Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation. J Cell Biol. 1999;144:161-73 pubmed
    ..These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements. ..
  7. Razzaque M, Soegiarto D, Chang D, Long F, Lanske B. Conditional deletion of Indian hedgehog from collagen type 2alpha1-expressing cells results in abnormal endochondral bone formation. J Pathol. 2005;207:453-61 pubmed
    Indian hedgehog (Ihh) is actively involved in endochondral bone formation...
  8. Stricker S, Fundele R, Vortkamp A, Mundlos S. Role of Runx genes in chondrocyte differentiation. Dev Biol. 2002;245:95-108 pubmed
  9. Iwasaki M, Le A, Helms J. Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis. Mech Dev. 1997;69:197-202 pubmed
    ..1997. The world according to hedgehog. Trends Genet. 13, 14-21). Two potential targets of Ihh are bmp6 and gli (Johnson et al., 1995...

More Information


  1. 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
    Indian hedgehog (Ihh) is indispensable for development of the osteoblast lineage in the endochondral skeleton...
  2. Gritli Linde A, Lewis P, McMahon A, Linde A. The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. Dev Biol. 2001;236:364-86 pubmed
    Sonic Hedgehog (Shh) and Indian Hedgehog (Ihh) are members of the Hedgehog (Hh) family of signaling molecules known to be involved in embryonic patterning and morphogenesis...
  3. Lanske B, Karaplis A, Lee K, Luz A, Vortkamp A, Pirro A, et al. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science. 1996;273:663-6 pubmed
    ..These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation. ..
  4. Bitgood M, McMahon A. Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol. 1995;172:126-38 pubmed
    The mouse Hedgehog gene family consists of three members, Sonic, Desert, and Indian hedgehog (Shh, Dhh, and Ihh, respectively), relatives of the Drosophila segment polarity gene, hedgehog (hh)...
  5. Yang Y, Topol L, Lee H, Wu J. Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development. 2003;130:1003-15 pubmed
    ..Wnt5a and Wnt5b regulate the transition between different chondrocyte zones independently of the Indian hedgehog (Ihh)/parathyroid hormone-related peptide (PTHrP) negative feedback loop...
  6. Inada M, Wang Y, Byrne M, Rahman M, Miyaura C, Lopez Otin C, et al. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc Natl Acad Sci U S A. 2004;101:17192-7 pubmed
    ..Cartilaginous growth plate abnormalities persisted in adult mice and phenocopied defects observed in human hereditary chondrodysplasias. Our findings demonstrate a unique role of Mmp13 in skeletal development. ..
  7. Brunet L, McMahon J, McMahon A, Harland R. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 1998;280:1455-7 pubmed
    ..Excess BMP activity in the absence of Noggin antagonism may enhance the recruitment of cells into cartilage, resulting in oversized growth plates; chondrocytes are also refractory to joint-inducing positional cues. ..
  8. Hammerschmidt M, Brook A, McMahon A. The world according to hedgehog. Trends Genet. 1997;13:14-21 pubmed
    ..Here, we review recent experiments addressing the function of the various Hedgehog members during invertebrate and vertebrate development. ..
  9. Yang X, Chen L, Xu X, Li C, Huang C, Deng C. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol. 2001;153:35-46 pubmed
    ..Without these inhibition signals, chondrocytes break quiescent state and undergo abnormal terminal differentiation, ultimately leading to osteoarthritis. ..
  10. Martinelli D, Fan C. Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes Dev. 2007;21:1231-43 pubmed
    ..Our data support a model in which GAS1 helps transform the Hedgehog protein gradient into the observed activity gradient. We propose that Gas1 is an evolutionarily novel, vertebrate-specific Hedgehog pathway regulator. ..
  11. Smits P, Li P, Mandel J, Zhang Z, Deng J, Behringer R, et al. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell. 2001;1:277-90 pubmed
    ..L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation. ..
  12. Echelard Y, Epstein D, St Jacques B, Shen L, Mohler J, McMahon J, et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993;75:1417-30 pubmed
    ..Ectopic expression of Shh in the mouse CNS leads to the activation of floor plate-expressed genes. These results suggest that Shh may play a role in the normal inductive interactions that pattern the ventral CNS. ..
  13. Baur S, Mai J, Dymecki S. Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. Development. 2000;127:605-19 pubmed
  14. Crick A, Babbs C, Brown J, Morriss Kay G. Developmental mechanisms underlying polydactyly in the mouse mutant Doublefoot. J Anat. 2003;202:21-6 pubmed
  15. Koziel L, Kunath M, Kelly O, Vortkamp A. Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev Cell. 2004;6:801-13 pubmed
    ..HS synthesis in mice carrying a hypomorphic mutation in Ext1 results in an elevated range of Indian hedgehog (Ihh) signaling during embryonic chondrocyte differentiation...
  16. Liu Z, Xu J, Colvin J, Ornitz D. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 2002;16:859-69 pubmed
    ..Signaling to multiple FGFRs positions FGF18 to coordinate chondrogenesis in the growth plate with osteogenesis in cortical and trabecular bone. ..
  17. Kobayashi T, Chung U, Schipani E, Starbuck M, Karsenty G, Katagiri T, et al. PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development. 2002;129:2977-86 pubmed
    ..Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-..
  18. Iwata T, Chen L, Li C, Ovchinnikov D, Behringer R, Francomano C, et al. A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos. Hum Mol Genet. 2000;9:1603-13 pubmed
    ..independent of unaltered expression of parathyroid hormone-related peptide (PTHrP) receptor and Indian Hedgehog (IHH:), suggesting a new regulatory role for Fgfr3 in embryos...
  19. Takabatake T, Ogawa M, Takahashi T, Mizuno M, Okamoto M, Takeshima K. Hedgehog and patched gene expression in adult ocular tissues. FEBS Lett. 1997;410:485-9 pubmed
    ..X-bhh, X-chh and mouse Ihh were detected in the iris and in the retinal pigment epithelium, while mouse Dhh was detected additionally in the ..
  20. Minina E, Kreschel C, Naski M, Ornitz D, Vortkamp A. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell. 2002;3:439-49 pubmed
    ..Using a limb culture system, we have analyzed the role of FGF signaling and its interaction with the Ihh/Pthlh and BMP pathways in regulating chondrocyte differentiation...
  21. Storm E, Kingsley D. GDF5 coordinates bone and joint formation during digit development. Dev Biol. 1999;209:11-27 pubmed
    ..Thus, GDF5 function in the digits demonstrates a link between cartilage development and joint development and is an important determinant of the pattern of bones and articulations in the digits. ..
  22. Chung U, Lanske B, Lee K, Li E, Kronenberg H. The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation. Proc Natl Acad Sci U S A. 1998;95:13030-5 pubmed
    ..Thus, the PTH/PTHrP receptor directly controls the pace and synchrony of chondrocyte differentiation and thereby coordinates development of the growth plate and adjacent bone. ..
  23. Kim J, Huang Z, Mo R. Gli3 null mice display glandular overgrowth of the developing stomach. Dev Dyn. 2005;234:984-91 pubmed
    ..In the developing stomach, Sonic (Shh) and Indian (Ihh) hedgehog are expressed in both distinct and overlapping regions...
  24. Lee C, Buttitta L, Fan C. Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite. Proc Natl Acad Sci U S A. 2001;98:11347-52 pubmed
    ..Taken together, these data suggest that GAS1 functions to reduce the availability of active SHH within the dorsal somite. ..
  25. Ueta C, Iwamoto M, Kanatani N, Yoshida C, Liu Y, Enomoto Iwamoto M, et al. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol. 2001;153:87-100 pubmed
    ..These data show that temporally and spatially regulated expression of Cbfa1 in chondrocytes is required for skeletogenesis, including formation of joints, permanent cartilages, and endochondral bones. ..
  26. Guo X, Mak K, Taketo M, Yang Y. The Wnt/beta-catenin pathway interacts differentially with PTHrP signaling to control chondrocyte hypertrophy and final maturation. PLoS ONE. 2009;4:e6067 pubmed publisher
    ..Furthermore, Wnt/beta-catenin signaling also controls final maturation of hypertrophic chondrocytes, but such regulation is PTHrP signaling-independent. ..
  27. Smits P, Dy P, Mitra S, Lefebvre V. Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J Cell Biol. 2004;164:747-58 pubmed
    ..They act, at least in part, by down-regulating Ihh signaling, Fgfr3, and Runx2 and by up-regulating Bmp6...
  28. Kim I, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80:159-70 pubmed
    ..Histology and in situ hybridization with probes for indian hedgehog (Ihh), collagen type X and osteopontin performed at E13.5, E14.5 and E17...
  29. Colnot C, de la Fuente L, Huang S, Hu D, Lu C, St Jacques B, et al. Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development. Development. 2005;132:1057-67 pubmed
    A null mutation in the morphogen Indian hedgehog (IHH) results in an embryonic lethal phenotype characterized by the conspicuous absence of bony tissue in the extremities...
  30. St Jacques B, Hammerschmidt M, McMahon A. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. 1999;13:2072-86 pubmed
    ..Indian hedgehog (Ihh) signaling from prehypertrophic chondrocytes has been implicated in the control of chondrocyte maturation by way of ..
  31. Jacob A, Smith C, Partanen J, Ornitz D. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev Biol. 2006;296:315-28 pubmed
    ..These data demonstrate that signaling through FGFR1 in osteoblasts is necessary to maintain the balance between bone formation and remodeling through a direct effect on osteoblast maturation. ..
  32. MacLean H, Guo J, Knight M, Zhang P, Cobrinik D, Kronenberg H. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest. 2004;113:1334-43 pubmed
    ..These studies suggest that the effects of PTHrP on both the rate and extent of chondrocyte proliferation are mediated, at least in part, through suppression of p57 expression. ..
  33. Yoshida C, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, et al. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 2004;18:952-63 pubmed
    ..Runx2(-/-)3(-/-) mice did not express Ihh, which regulates chondrocyte proliferation and maturation...
  34. Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, et al. Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem. 2005;280:19185-95 pubmed
  35. Kobayashi T, Soegiarto D, Yang Y, Lanske B, Schipani E, McMahon A, et al. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest. 2005;115:1734-42 pubmed
    ..Parathyroid hormone-related (PTH-related) protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, thereby maintaining the length of columns...
  36. Grashoff C, Aszodi A, Sakai T, Hunziker E, Fassler R. Integrin-linked kinase regulates chondrocyte shape and proliferation. EMBO Rep. 2003;4:432-8 pubmed
    ..These findings suggest that Ilk regulates actin reorganization in chondrocytes and modulates chondrocyte growth independently of phosphorylation of Pkb/Akt and GSK3-beta. ..
  37. Goodrich L, Johnson R, Milenkovic L, McMahon J, Scott M. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev. 1996;10:301-12 pubmed
    ..As in flies, mouse ptc transcription appears to be indicative of hedgehog signal reception. The results support the existence of a conserved signaling pathway used for pattern formation in insects and mammals. ..
  38. Purcell P, Joo B, Hu J, Tran P, Calicchio M, O Connell D, et al. Temporomandibular joint formation requires two distinct hedgehog-dependent steps. Proc Natl Acad Sci U S A. 2009;106:18297-302 pubmed publisher
    ..Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ. ..
  39. Robledo R, Rajan L, Li X, Lufkin T. The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev. 2002;16:1089-101 pubmed
    ..Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth. ..
  40. Cobb J, Dierich A, Huss Garcia Y, Duboule D. A mouse model for human short-stature syndromes identifies Shox2 as an upstream regulator of Runx2 during long-bone development. Proc Natl Acad Sci U S A. 2006;103:4511-5 pubmed
    ..Furthermore, using this mouse model, we establish the cellular etiology of these defects and show that Shox2 acts upstream the Runx2 gene, a key regulator of chondrogenesis. ..
  41. Koziel L, Wuelling M, Schneider S, Vortkamp A. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development. 2005;132:5249-60 pubmed
    During endochondral ossification, the secreted growth factor Indian hedgehog (Ihh) regulates several differentiation steps...
  42. Blitz E, Viukov S, Sharir A, Shwartz Y, Galloway J, Pryce B, et al. Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell. 2009;17:861-73 pubmed publisher
    ..This study establishes a mechanistic basis for tendon-skeleton regulatory interactions during musculoskeletal assembly and bone secondary patterning. ..
  43. Kolterud A, Grosse A, Zacharias W, Walton K, Kretovich K, Madison B, et al. Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning. Gastroenterology. 2009;137:618-28 pubmed publisher
    ..Cellular targets were identified by immunostaining. Ihh-overexpressing transgenic animals were generated and analyzed...
  44. Naski M, Colvin J, Coffin J, Ornitz D. Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 1998;125:4977-88 pubmed
    ..Significantly, FGFR3 downregulated the Indian hedgehog (Ihh) signaling pathway and Bmp4 expression in both growth plate chondrocytes and in the perichondrium...
  45. Bendall A, Hu G, Levi G, Abate Shen C. Dlx5 regulates chondrocyte differentiation at multiple stages. Int J Dev Biol. 2003;47:335-44 pubmed
  46. Joeng K, Long F. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development. 2009;136:4177-85 pubmed publisher
    Indian hedgehog (Ihh) critically regulates multiple aspects of endochondral bone development...
  47. Hirata M, Kugimiya F, Fukai A, Ohba S, Kawamura N, Ogasawara T, et al. C/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57. PLoS ONE. 2009;4:e4543 pubmed publisher
  48. Hayes C, Rump A, Cadman M, Harrison M, Evans E, Lyon M, et al. A high-resolution genetic, physical, and comparative gene map of the doublefoot (Dbf) region of mouse chromosome 1 and the region of conserved synteny on human chromosome 2q35. Genomics. 2001;78:197-205 pubmed
    ..These genes include those encoding known developmental signaling molecules such as WNT proteins and IHH, and we provide evidence that these genes are candidates for the Dbf mutation.
  49. Lu J, Lian G, Lenkinski R, De Grand A, Vaid R, Bryce T, et al. Filamin B mutations cause chondrocyte defects in skeletal development. Hum Mol Genet. 2007;16:1661-75 pubmed
    ..These data suggest that disruption of the ECM-beta1-integrin-Flnb pathway contributes to defects in vertebral and distal limb development, similar to those seen in the human autosomal recessive SCT due to Flnb mutations. ..
  50. Ivkovic S, Yoon B, Popoff S, Safadi F, Libuda D, Stephenson R, et al. Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development. 2003;130:2779-91 pubmed
    ..These results demonstrate that CTGF is important for cell proliferation and matrix remodeling during chondrogenesis, and is a key regulator coupling extracellular matrix remodeling to angiogenesis at the growth plate. ..
  51. Ramalho Santos M, Melton D, McMahon A. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000;127:2763-72 pubmed
    ..These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations. ..
  52. Svärd J, Heby Henricson K, Henricson K, Persson Lek M, Rozell B, Lauth M, et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell. 2006;10:187-97 pubmed
    ..Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway. ..
  53. 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
    Indian hedgehog (Ihh), one of the three mammalian hedgehog (Hh) proteins, coordinates proliferation and differentiation of chondrocytes during endochondral bone development...
  54. Hill T, Später D, Taketo M, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8:727-38 pubmed
    ..Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes. ..
  55. Minina E, Wenzel H, Kreschel C, Karp S, Gaffield W, McMahon A, et al. BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development. 2001;128:4523-34 pubmed
    During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of ..
  56. Inada M, Yasui T, Nomura S, Miyake S, Deguchi K, Himeno M, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999;214:279-90 pubmed
    ..These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation. ..
  57. Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, et al. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet. 2000;24:391-5 pubmed
    ..Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis. ..
  58. Maeda Y, Nakamura E, Nguyen M, Suva L, Swain F, Razzaque M, et al. Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone. Proc Natl Acad Sci U S A. 2007;104:6382-7 pubmed
    Indian hedgehog (Ihh) is essential for chondrocyte and osteoblast proliferation/differentiation during prenatal endochondral bone formation...
  59. Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest. 2004;113:188-99 pubmed
    ..These findings indicate that the insoluble VEGF(188) isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation...
  60. Arikawa Hirasawa E, Watanabe H, Takami H, Hassell J, Yamada Y. Perlecan is essential for cartilage and cephalic development. Nat Genet. 1999;23:354-8 pubmed
    ..Our findings suggest that these molecules affect similar signalling pathways. ..
  61. Rossi F, MacLean H, Yuan W, Francis R, Semenova E, Lin C, et al. p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development. Dev Biol. 2002;247:271-85 pubmed
    ..The results suggest that Cbfa1 links a p107- and p130-mediated cell cycle arrest to chondrocyte terminal differentiation. ..
  62. Eswarakumar V, Monsonego Ornan E, Pines M, Antonopoulou I, Morriss Kay G, Lonai P. The IIIc alternative of Fgfr2 is a positive regulator of bone formation. Development. 2002;129:3783-93 pubmed
    ..A decrease in the domain of transcription of the chondrocyte markers Ihh and PTHrP (Pthlh) corresponded with a decrease in their transcripts in the proliferative and hypertrophic ..
  63. Mak K, Kronenberg H, Chuang P, Mackem S, Yang Y. Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development. 2008;135:1947-56 pubmed publisher
    ..Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative ..
  64. Rokutanda S, Fujita T, Kanatani N, Yoshida C, Komori H, Liu W, et al. Akt regulates skeletal development through GSK3, mTOR, and FoxOs. Dev Biol. 2009;328:78-93 pubmed publisher
  65. Yu L, Liu H, Yan M, Yang J, Long F, Muneoka K, et al. Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton. Dev Biol. 2007;306:549-59 pubmed
    ..of Runx2 and Runx3 could account for the lack of chondrocyte hypertrophy, while a down-regulation of Ihh expression may be responsible for a significant reduction in chondrocyte proliferation in the mutant stylopod...
  66. Chen X, Macica C, Nasiri A, Broadus A. Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone-related protein in mice. Arthritis Rheum. 2008;58:3788-97 pubmed publisher
    Chondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (IHH)-parathyroid hormone-related protein (PTHrP) axis...
  67. Vortkamp A, Lee K, Lanske B, Segre G, Kronenberg H, Tabin C. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science. 1996;273:613-22 pubmed
    ..A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now ..
  68. Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itoh N, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16:870-9 pubmed
    ..Conversely, chondrocyte proliferation and the number of differentiated chondrocytes are increased. Therefore, FGF18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis. ..
  69. Amano K, Ichida F, Sugita A, Hata K, Wada M, Takigawa Y, et al. MSX2 stimulates chondrocyte maturation by controlling Ihh expression. J Biol Chem. 2008;283:29513-21 pubmed publisher
    ..In addition, caMsx2 overexpression induced Ihh (Indian hedgehog) expression in mouse primary chondrocytes...
  70. Yang Y, Guillot P, Boyd Y, Lyon M, McMahon A. Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling. Development. 1998;125:3123-32 pubmed
    ..In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud...
  71. Takeda S, Bonnamy J, Owen M, Ducy P, Karsenty G. Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. Genes Dev. 2001;15:467-81 pubmed
    ..These results identify Cbfa1 as a hypertrophic chondrocyte differentiation factor and provide a genetic argument for a common regulation of osteoblast and chondrocyte differentiation mediated by Cbfa1. ..
  72. Hilton M, Tu X, Cook J, Hu H, Long F. Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development. Development. 2005;132:4339-51 pubmed
    Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization...
  73. Boulet A, Capecchi M. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Development. 2004;131:299-309 pubmed
    ..As a consequence, growth and maturation of these bones is highly disorganized, resulting in the creation of amorphous bony elements, rather than a normal radius and ulna. ..
  74. Acampora D, Merlo G, Paleari L, Zerega B, Postiglione M, Mantero S, et al. Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development. 1999;126:3795-809 pubmed
    ..The defects observed in Dlx5-/- mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation. ..
  75. Karp S, Schipani E, St Jacques B, Hunzelman J, Kronenberg H, McMahon A. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development. 2000;127:543-8 pubmed
    Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton...