Gene Symbol: Gdf5
Description: growth differentiation factor 5
Alias: BMP-14, Cdmp-1, brp, growth/differentiation factor 5, bone morphogenetic protein 14, cartilage-derived morphogenetic protein-1
Species: mouse
Products:     Gdf5

Top Publications

  1. Owens E, Solursh M. Accelerated maturation of limb mesenchyme by the BrachypodH mouse mutation. Differentiation. 1983;24:145-8 pubmed
  2. Storm E, Huynh T, Copeland N, Jenkins N, Kingsley D, Lee S. Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature. 1994;368:639-43 pubmed
    ..factors (GDF) 5,6 and 7) and show by mapping, expression patterns and sequencing that mutations in Gdf5 are responsible for skeletal alterations in bp mice...
  3. Yi S, Daluiski A, Pederson R, Rosen V, Lyons K. The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Development. 2000;127:621-30 pubmed
    ..Analyses of BmprIB and Gdf5 single mutants, as well as BmprIB; Gdf5 double mutants suggests that GDF5 is a ligand for BMPRIB in vivo...
  4. Meech R, Edelman D, Jones F, Makarenkova H. The homeobox transcription factor Barx2 regulates chondrogenesis during limb development. Development. 2005;132:2135-46 pubmed
    ..We also found that two members of the BMP family that are crucial for chondrogenesis, GDF5 and BMP4, regulate the pattern of Barx2 expression in developing limbs...
  5. Schwaerzer G, Hiepen C, Schrewe H, Nickel J, Ploeger F, Sebald W, et al. New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. J Bone Miner Res. 2012;27:429-42 pubmed publisher
    Growth and differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) family, is essential for cartilage, bone, and joint formation...
  6. 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. ..
  7. Dy P, Smits P, Silvester A, Penzo Méndez A, Dumitriu B, Han Y, et al. Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage. Dev Biol. 2010;341:346-59 pubmed publisher
    ..We show that joint development aborts early in complete mutants (Sox5(-/-)6(-/-)). Gdf5 and Wnt9a expression is punctual in articular progenitor cells, but Sox9 downregulation and cell condensation in ..
  8. Chang S, Hoang B, Thomas J, Vukicevic S, Luyten F, Ryba N, et al. Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J Biol Chem. 1994;269:28227-34 pubmed
  9. Storm E, Kingsley D. Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. Development. 1996;122:3969-79 pubmed
    ..brachypodism locus encodes a bone morphogenetic protein (BMP)-like molecule called growth/differentiation factor 5 (GDF5)...

More Information


  1. 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. ..
  2. Masuya H, Nishida K, Furuichi T, Toki H, Nishimura G, Kawabata H, et al. A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice. Hum Mol Genet. 2007;16:2366-75 pubmed
    Growth and differentiation factor 5 (GDF5) has been implicated in chondrogenesis and joint formation, and an association of GDF5 and osteoarthritis (OA) has been reported recently...
  3. Tucker A, Watson R, Lettice L, Yamada G, Hill R. Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Development. 2004;131:1235-45 pubmed
    ..role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation.
  4. Settle S, Rountree R, Sinha A, Thacker A, Higgins K, Kingsley D. Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Dev Biol. 2003;254:116-30 pubmed
    Growth/differentiation factors 5, 6, and 7 (GDF5/6/7) represent a distinct subgroup within the bone morphogenetic protein (BMP) family of secreted signaling molecules...
  5. Storm E, Kingsley D. GDF5 coordinates bone and joint formation during digit development. Dev Biol. 1999;209:11-27 pubmed
    ..One member of this family, Growth/differentiation factor 5 (GDF5), is encoded by the mouse brachypodism locus...
  6. Daans M, Luyten F, Lories R. GDF5 deficiency in mice is associated with instability-driven joint damage, gait and subchondral bone changes. Ann Rheum Dis. 2011;70:208-13 pubmed publisher
    A functional polymorphism leading to reduced levels of growth and differentiation factor 5 (GDF5) was recently identified as a susceptibility factor for osteoarthritis...
  7. Seemann P, Schwappacher R, Kjaer K, Krakow D, Lehmann K, Dawson K, et al. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 2005;115:2373-81 pubmed
    Here we describe 2 mutations in growth and differentiation factor 5 (GDF5) that alter receptor-binding affinities...
  8. Guo X, Day T, Jiang X, Garrett Beal L, Topol L, Yang Y. Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev. 2004;18:2404-17 pubmed
    ..Wnt4, Wnt14, and Wnt16 may play redundant roles in synovial joint induction by signaling through the beta-catenin-mediated canonical Wnt pathway. ..
  9. 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. ..
  10. 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
    ..b>GDF5 is a BMP-related signal, which is also required for proper digit formation...
  11. Wilson D, Phamluong K, Lin W, Barck K, Carano R, Diehl L, et al. Chondroitin sulfate synthase 1 (Chsy1) is required for bone development and digit patterning. Dev Biol. 2012;363:413-25 pubmed publisher
    ..Our results place Chsy1 as an essential regulator of joint patterning and provide a mouse model of human brachydactylies caused by mutations in CHSY1. ..
  12. Mangiavini L, Merceron C, Araldi E, Khatri R, Gerard O Riley R, Wilson T, et al. Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development. Dev Biol. 2014;393:124-36 pubmed publisher
    ..Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements. ..
  13. Pei Z, Yang Y, Kiess W, Sun C, Luo F. Dynamic profile and adipogenic role of growth differentiation factor 5 (GDF5) in the differentiation of 3T3-L1 preadipocytes. Arch Biochem Biophys. 2014;560:27-35 pubmed publisher
    ..Recent studies have shown that growth differentiation factor-5 (GDF5) promotes brown adipogenesis, however its role in white adipogenesis is still uncertain...
  14. Hinoi E, Iezaki T, Ozaki K, Yoneda Y. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate. Biochem Biophys Res Commun. 2014;452:974-9 pubmed publisher
    ..of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis...
  15. Liu J, Saito K, Maruya Y, Nakamura T, Yamada A, Fukumoto E, et al. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation. Sci Rep. 2016;6:23670 pubmed publisher
    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to ..
  16. Harfe B, McManus M, Mansfield J, Hornstein E, Tabin C. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A. 2005;102:10898-903 pubmed
    ..Thus, Dicer is required for the formation of normal mouse limbs. Strikingly, however, we did not detect defects in basic patterning or in tissue-specific differentiation of Dicer-deficient limb buds. ..
  17. Chen H, Capellini T, Schoor M, Mortlock D, Reddi A, Kingsley D. Heads, Shoulders, Elbows, Knees, and Toes: Modular Gdf5 Enhancers Control Different Joints in the Vertebrate Skeleton. PLoS Genet. 2016;12:e1006454 pubmed publisher
    ..Growth and differentiation factor 5 (Gdf5) is one of the earliest markers of joint formation, is required for normal joint development in both mice and ..
  18. Brown K. The comparative biology of chondrodysplasias in mice. Pathol Immunopathol Res. 1988;7:55-61 pubmed
    ..The systematic study of these disturbed developmental and biochemical pathways will increase our understanding of chondrogenesis and chondrodysplasia as similar studies have done for intermediary metabolism. ..
  19. 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. ..
  20. Katsu K, Tokumori D, Tatsumi N, Suzuki A, Yokouchi Y. BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo. Dev Biol. 2012;363:15-26 pubmed publisher
    ..Our data indicate that Dan plays an essential role in the establishment of the L-R axis by inhibiting BMP signaling around the node...
  21. Garciadiego Cázares D, Aguirre Sánchez H, Abarca Buis R, Kouri J, Velasquillo C, Ibarra C. Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis. PLoS ONE. 2015;10:e0127166 pubmed publisher
    ..Members of the Transforming growth factor beta (Tgf-β) Superfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could ..
  22. Toyran S, Lin A, Edward D. Expression of growth differentiation factor-5 and bone morphogenic protein-7 in intraocular osseous metaplasia. Br J Ophthalmol. 2005;89:885-90 pubmed
    ..0162). The increase in GDF-5, BMP-7, and TGF beta1 immunoreactivity in zones of RPE metaplasia in eyes with osseous metaplasia suggests that these proteins have an important role in intraocular ectopic bone formation. ..
  23. Tylzanowski P, Mebis L, Luyten F. The Noggin null mouse phenotype is strain dependent and haploinsufficiency leads to skeletal defects. Dev Dyn. 2006;235:1599-607 pubmed
    ..Furthermore, we have discovered Noggin haploinsufficiency leading to carpal and tarsal fusions reminiscent of some phenotypes reported for NOGGIN haploinsufficiency in humans. ..
  24. Stricker S, Fundele R, Vortkamp A, Mundlos S. Role of Runx genes in chondrocyte differentiation. Dev Biol. 2002;245:95-108 pubmed
  25. Tavella S, Biticchi R, Morello R, Castagnola P, Musante V, Costa D, et al. Forced chondrocyte expression of sonic hedgehog impairs joint formation affecting proliferation and apoptosis. Matrix Biol. 2006;25:389-97 pubmed
    ..Molecular markers of joints, such as Gdf5 and sFrp2 were absent at presumptive joint sites and Tenascin C, a molecule associated with joint formation and ..
  26. Tocharus J, Tsuchiya A, Kajikawa M, Ueta Y, Oka C, Kawaichi M. Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling. Dev Growth Differ. 2004;46:257-74 pubmed
    ..All these data suggest that HtrA3 and -1 have the overlapping biological activities but can function in complementary fashion in certain types of tissues. ..
  27. Hwang C, Wu D. Noggin heterozygous mice: an animal model for congenital conductive hearing loss in humans. Hum Mol Genet. 2008;17:844-53 pubmed
    ..consequence of chondrocyte hyperplasia due to unopposed Bmp activities in these mutants such as Bmp4 and Bmp14 (Gdf5)...
  28. Gao B, Hu J, Stricker S, Cheung M, Ma G, Law K, et al. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature. 2009;458:1196-200 pubmed publisher
    ..Furthermore, we show that in a mouse model that recapitulates the E95K mutation, there is a change in the potency and range of signalling. The mice have digit abnormalities consistent with the human disorder. ..
  29. Liu Z, Shen J, Pu K, Katus H, Plöger F, Tiefenbacher C, et al. GDF5 and BMP2 inhibit apoptosis via activation of BMPR2 and subsequent stabilization of XIAP. Biochim Biophys Acta. 2009;1793:1819-27 pubmed publisher
    b>GDF5 and BMP2, members of the TGF-beta superfamily of growth factors, are known to regulate apoptosis in different cell types either positively or negatively...
  30. Hyde G, Dover S, Aszodi A, Wallis G, Boot Handford R. Lineage tracing using matrilin-1 gene expression reveals that articular chondrocytes exist as the joint interzone forms. Dev Biol. 2007;304:825-33 pubmed
  31. Chen Y, Knezevic V, Ervin V, Hutson R, Ward Y, Mackem S. Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh. Development. 2004;131:2339-47 pubmed
    ..The resulting altered balance between 'effective' Gli3 activating and repressing functions may also serve to extend the Shh activity gradient spatially or temporally...
  32. Takahashi Y, Yasuhiko Y, Takahashi J, Takada S, Johnson R, Saga Y, et al. Metameric pattern of intervertebral disc/vertebral body is generated independently of Mesp2/Ripply-mediated rostro-caudal patterning of somites in the mouse embryo. Dev Biol. 2013;380:172-84 pubmed publisher
    ..Therefore, we propose that rostro-caudal patterning of somites is not a prerequisite for metameric patterning of the IVD and VB, but instead required to stimulate IVD differentiation in the caudal half of the sclerotome. ..
  33. Witte F, Chan D, Economides A, Mundlos S, Stricker S. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) and Indian hedgehog regulate digit outgrowth mediated by the phalanx-forming region. Proc Natl Acad Sci U S A. 2010;107:14211-6 pubmed publisher
  34. Osório C, Chacón P, Kisiswa L, White M, Wyatt S, Rodríguez Tébar A, et al. Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development. Development. 2013;140:4751-62 pubmed publisher
    ..Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor Î..
  35. Schreuder H, Liesum A, Pohl J, Kruse M, Koyama M. Crystal structure of recombinant human growth and differentiation factor 5: evidence for interaction of the type I and type II receptor-binding sites. Biochem Biophys Res Commun. 2005;329:1076-86 pubmed
    The crystal structure of human growth differentiation factor 5 (GDF5) was solved at 2.4A resolution...
  36. Perez W, Weller C, Shou S, Stadler H. Survival of Hoxa13 homozygous mutants reveals a novel role in digit patterning and appendicular skeletal development. Dev Dyn. 2010;239:446-57 pubmed publisher
    ..Characterization of prochondrogenic genes in the affected carpal/tarsal regions revealed significant reduction in Gdf5 expression, whereas Bmp2 expression was significantly elevated...
  37. Lee K, Mendelsohn M, Jessell T. Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev. 1998;12:3394-407 pubmed
    ..More generally, these results suggest that BMP signaling may have a prominent role in the assignment of neuronal identity within the mammalian CNS. ..
  38. Hinoi E, Nakamura Y, Takada S, Fujita H, Iezaki T, Hashizume S, et al. Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure. Diabetes. 2014;63:162-75 pubmed publisher
    Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis in mammals, little is known about its functionality in adipogenesis and energy homeostasis...
  39. Konyukhov B, Ginter E. A study of the action of the brachypodism-H gene on development of the long bones of the hind limbs in the mouse. Folia Biol (Praha). 1966;12:199-206 pubmed
  40. Zhao Y, Zhang M, Liu H, Wang J. Signaling by growth/differentiation factor 5 through the bone morphogenetic protein receptor type IB protects neurons against kainic acid-induced neurodegeneration. Neurosci Lett. 2017;651:36-42 pubmed publisher
    ..Thus, we conclude that GDF-5 protects hippocampal neurons against KA-induced neurodegeneration by signaling through BMPRIB, suggesting a therapeutic potential for GDF-5 in neurodegenerative diseases. ..
  41. Zhou W, Zhu H, Zhao J, Li H, Wan Y, Cao J, et al. Misexpression of Pknox2 in mouse limb bud mesenchyme perturbs zeugopod development and deltoid crest formation. PLoS ONE. 2013;8:e64237 pubmed publisher
  42. Bobacz K, Sunk I, Hayer S, Amoyo L, Tohidast Akrad M, Kollias G, et al. Differentially regulated expression of growth differentiation factor 5 and bone morphogenetic protein 7 in articular cartilage and synovium in murine chronic arthritis: potential importance for cartilage breakdown and synovial hypertrophy. Arthritis Rheum. 2008;58:109-18 pubmed publisher
    To examine whether the endogenous expression of growth differentiation factor 5 (GDF-5) and bone morphogenetic protein 7 (BMP-7) is altered in the cartilage and synovium of human tumor necrosis factor alpha (TNFalpha)-transgenic (hTNFtg) ..
  43. Yang J, Qin S, Yi C, Ma G, Zhu H, Zhou W, et al. MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation. FEBS Lett. 2011;585:2992-7 pubmed publisher
    ..Collectively, our findings expand our understanding of the transcriptional regulation and the chondrogenic role of miR-140 in chondrogenesis. ..
  44. Suto J. Identification of mutation in the growth differentiation factor 5 (Gdf5) gene in NC-brp/brp mice. J Vet Med Sci. 2006;68:1121-4 pubmed
    ..A series of bp mutations are due to defects in the growth differentiation factor 5 (Gdf5) gene...
  45. Oka C, Tsujimoto R, Kajikawa M, Koshiba Takeuchi K, Ina J, Yano M, et al. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Development. 2004;131:1041-53 pubmed
    ..The GST-pulldown assay showed that HtrA1 binds to a broad range of Tgfbeta family proteins, including Bmp4, Gdf5, Tgfbetas and activin...
  46. Dyment N, Breidenbach A, Schwartz A, Russell R, Aschbacher Smith L, Liu H, et al. Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis. Dev Biol. 2015;405:96-107 pubmed publisher
    ..The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis...
  47. Spagnoli A, O Rear L, Chandler R, Granero Molto F, Mortlock D, Gorska A, et al. TGF-beta signaling is essential for joint morphogenesis. J Cell Biol. 2007;177:1105-17 pubmed
    ..We propose a model for joint development in which TGF-beta signaling represents a means of entry to initiate the process. ..
  48. Rhodes R, Elmer W. Aberrant metabolism of matrix components in neonatal fibular cartilage of brachypod (bpH) mice. Dev Biol. 1975;46:14-27 pubmed
  49. Andrews S, Peters J. Linkage analyses and biochemical genetics of sorbitol dehydrogenase-1 (Sdh-1) in the mouse. Biochem Genet. 1983;21:809-17 pubmed
    ..9 +/- 1.4--pa--16.4 +/- 3.6--a--3.9 +/- 1.9--bp. ..
  50. Yamaguchi T, Bradley A, McMahon A, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126:1211-23 pubmed
    ..The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells. ..
  51. Williamson C, Beechey C, Papworth D, Wroe S, Wells C, Cobb L, et al. Imprinting of distal mouse chromosome 2 is associated with phenotypic anomalies in utero. Genet Res. 1998;72:255-65 pubmed
    ..A preliminary conclusion is that there is neither growth enhancement in PatDp.dist2 nor growth retardation in MatDp.dist2 offspring. ..
  52. Kumar M, Syed S, Taketo M, Tanwar P. Epithelial Wnt/βcatenin signalling is essential for epididymal coiling. Dev Biol. 2016;412:234-49 pubmed publisher
    ..In summary, our work has established that epithelial canonical Wnt signalling is a critical regulator of WD coiling and its precise regulation is essential for WD/epididymal differentiation. ..
  53. Shin J, Ankamreddy H, Jakka N, Lee S, Kim U, Bok J. Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear. Int J Dev Biol. 2017;61:557-563 pubmed publisher
    ..These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development. ..
  54. Huang B, Trofka A, Furusawa A, Norrie J, Rabinowitz A, Vokes S, et al. An interdigit signalling centre instructs coordinate phalanx-joint formation governed by 5'Hoxd-Gli3 antagonism. Nat Commun. 2016;7:12903 pubmed publisher
    ..We propose that 5'Hoxd genes and Gli3 are part of an interdigital signalling centre that sets net Bmp signalling levels from different interdigits to coordinately regulate phalanx and joint formation. ..
  55. Laue K, Pogoda H, Daniel P, van Haeringen A, Alanay Y, von Ameln S, et al. Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid. Am J Hum Genet. 2011;89:595-606 pubmed publisher
    ..This work reveals a physiological role for RA in partitioning skeletal elements and in the maintenance of cranial suture patency. ..
  56. Cai T, Yang L, Cai W, Guo S, Yu P, Li J, et al. Dysplastic spondylolysis is caused by mutations in the diastrophic dysplasia sulfate transporter gene. Proc Natl Acad Sci U S A. 2015;112:8064-9 pubmed publisher
    ..The analysis of the gene-disease network may shed new light on the study of patients with dysplastic spondylolysis and spondylolisthesis as well as high-risk individuals who are asymptomatic. ..
  57. Zhao H, Zhou W, Yao Z, Wan Y, Cao J, Zhang L, et al. Foxp1/2/4 regulate endochondral ossification as a suppresser complex. Dev Biol. 2015;398:242-54 pubmed publisher
  58. Bhattaram P, Penzo Méndez A, Kato K, Bandyopadhyay K, Gadi A, Taketo M, et al. SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis. J Cell Biol. 2014;207:657-71 pubmed publisher
    ..This synergy may determine cell fate in many processes besides skeletogenesis. ..
  59. Hinoi E, Iezaki T, Fujita H, Watanabe T, Odaka Y, Ozaki K, et al. PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway. Biochem Biophys Res Commun. 2014;450:255-60 pubmed publisher
    We have previously demonstrated promotion by growth differentiation factor-5 (GDF5) of brown adipogenesis for systemic energy expenditure through a mechanism relevant to activating the bone morphological protein (BMP) receptor/mothers ..
  60. Delpretti S, Montavon T, Leleu M, Joye E, Tzika A, Milinkovitch M, et al. Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding. Cell Rep. 2013;5:137-50 pubmed publisher
    ..In this context, we discuss the implementation of a common "budding toolkit" between the cecum and the limbs. ..
  61. Goto N, Imamura K, Sakamoto K. [Inheritance and growth of mouse mutation brachypodism (brp) (author's transl)]. Jikken Dobutsu. 1977;26:231-8 pubmed
    ..1. From the results of crossing tests, it might be concluded that an autosomal recessive gene (brp, linkage group V) was responsible for the occurrence of the brachypodism. 2...
  62. Chiang C, Litingtung Y, Harris M, Simandl B, Li Y, Beachy P, et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol. 2001;236:421-35 pubmed
    ..Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity...
  63. Nakahara T, Tominaga K, Koseki T, Yamamoto M, Yamato K, Fukuda J, et al. Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad. Cell Signal. 2003;15:181-7 pubmed
    ..Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells. ..
  64. Barna M, Pandolfi P, Niswander L. Gli3 and Plzf cooperate in proximal limb patterning at early stages of limb development. Nature. 2005;436:277-81 pubmed
    ..The initial division of the vertebrate limb into two distinct molecular domains is consistent with fossil evidence indicating that the upper and lower extremities of the limb have different evolutionary origins. ..
  65. Daans M, Lories R, Luyten F. Absence of GDF5 does not interfere with LPS Toll-like receptor signaling. Clin Exp Rheumatol. 2009;27:495-8 pubmed
    Growth and differentiation factor 5 (GDF5), member of TGFBeta superfamily, has been implicated in limb development, and is known to play an important role in joint formation...
  66. GRUNEBERG H, Lee A. The anatomy and development of brachypodism in the mouse. J Embryol Exp Morphol. 1973;30:119-41 pubmed
  67. Shwartz Y, Viukov S, Krief S, Zelzer E. Joint Development Involves a Continuous Influx of Gdf5-Positive Cells. Cell Rep. 2016;15:2577-87 pubmed publisher
    ..All of these compartments are commonly assumed to originate from an early set of Gdf5-expressing progenitors populating the interzone domain...
  68. Williamson C, Beechey C, Ball S, Dutton E, Cattanach B, Tease C, et al. Localisation of the imprinted gene neuronatin, Nnat, confirms and refines the location of a second imprinting region on mouse chromosome 2. Cytogenet Cell Genet. 1998;81:73-8 pubmed
    ..It maps close to agouti, some alleles of which show differential expression according to parental origin. The localisation of Nnat to band H1 confirms and refines the map location of a second imprinting region on mouse Chr 2. ..
  69. Houweling A, Dildrop R, Peters T, Mummenhoff J, Moorman A, Ruther U, et al. Gene and cluster-specific expression of the Iroquois family members during mouse development. Mech Dev. 2001;107:169-74 pubmed
    ..The results indicate that the Irx genes are coordinately regulated at the level of the cluster. ..
  70. Eyal S, Blitz E, Shwartz Y, Akiyama H, Schweitzer R, Zelzer E. On the development of the patella. Development. 2015;142:1831-9 pubmed publisher
  71. Niedermaier M, Schwabe G, Fees S, Helmrich A, Brieske N, Seemann P, et al. An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression. J Clin Invest. 2005;115:900-9 pubmed
    ..upregulation of hedgehog target genes such as Gli1-3, patched, and Pthlh, as well as the downregulation of Ihh and Gdf5. This results in shortening of the digits through an arrest of chondrocyte differentiation and the disruption of ..
  72. Dathe K, Kjaer K, Brehm A, Meinecke P, Nurnberg P, Neto J, et al. Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. Am J Hum Genet. 2009;84:483-92 pubmed publisher the Bone morphogenetic protein receptor 1B (BMPR1B) or in its ligand Growth and differentiation factor 5 (GDF5). A linkage analysis performed in a mutation-negative family identified a novel locus for BDA2 on chromosome 20p12...
  73. Shung C, Ota S, Zhou Z, Keene D, Hurlin P. Disruption of a Sox9-?-catenin circuit by mutant Fgfr3 in thanatophoric dysplasia type II. Hum Mol Genet. 2012;21:4628-44 pubmed publisher
  74. Kugimiya F, Kawaguchi H, Kamekura S, Chikuda H, Ohba S, Yano F, et al. Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation. J Biol Chem. 2005;280:35704-12 pubmed
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