Abstract
Embryonic development and tissue regeneration is based on cell communications by conserved families of signaling molecules, such as Dpp/BMP, Wnt, FGF, Nodal and Hedgehog. The vertebrate bone morphogenetic proteins (BMPs) are involved in the development of nearly all organs and tissues (Fig. 1), including the nervous system, somites, lung, kidney, skin and gonads, as well as in critical steps in the establishment of the basic embryonic body plan [1].
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References
Hogan BLM (1996) Bone morphogenetic proteins-multifunctional regulators of verte-brate development. Gen Develop 10: 1580–1594
Wolpert L, Beddington R, Brockes J, Jessell T, Lawrence P, Meyerowitz E (1998) Pat-terning of the vertebrate body plan I: axes and germ layers. In: L Wolpert (ed): Principles of development. Current Biology Ltd, London, 61–96
Lemaire P, Yasuo H (1998) Developmental signalling: A careful balancing act. Curr Biol 8: 228–231
Schier AF (2001) Axis formation and pattering in zebrafish. Curr Op Gen Develop 11: 393–404
Zhao GQ (2003) Consequences of knocking out BMP signalling in the mouse. Genesis 35: 43–56
DeRobertis EM, Sasai Y (1996) A common plan for dorsoventral patterning in Bilateria. Nature 380: 37–40
Mullins MC, Hammerschmidt M, Kane DA, Odenthal J, Brand M, van Eeden FJ, Furutani-Seiki M, Granato M, Haffter P, Heisenberg CP et al (1996) Genes establishing dorsoventral pattern formation in the zebrafish embryo: the ventral specifying genes. Development 123: 81–93
Blader P, Rastegar S, Fischer N, Strahle U (1997) Cleavage of the BMP-4 antagonist chordin by zebrafish tolloid. Science 278: 1937–1940
Wolpert L, Beddington R, Brockes J, Jessell T, Lawrence P, Meyerowitz E (1998) Pat-terning of the vertebrate body plan II: the mesoderm and early nervous system. In: L Wolpert (ed): Principles of development. Current Biology Ltd, London, 97–124
Yamaguchi TP (2001) Heads or tails: Wnts and anterior-posterior patterning. Curr Biol 11: 713–724
Meno C, Saijoh Y, Fujii H, Ikeda M, Yokoyam M, Toyoda Y, Hamada H (1996) Left-right asymmetric expression of the TGFP-family member lefty in mouse embryos. Nature 381: 151–155
Whitman M, Mercola M (2001) TGF-I3 superfamily signalling and left-right asymmetry. Sci STKE 64: 1–7
Mehler MF, Mabie PC, Zhang D, Kessler JA (1997). Bone morphogenetic proteins in the nervous system. Trends Neurosci 20: 309–317
Wilson PA, Hemmati-Brivanlou A (1995) Induction of epidermis and inhibition of neural fate by BMP-4. Nature 376: 331–333
Liem JKF, tremmal G, Roelink H, Jessel TM (1995) Dorsal differentiation of neural plate cells induced by Bmp-mediated signals from epidermal ectoderm. Cell 82: 969–976
Lein P, Drahushuk KM, Higgins D (2002) Effects of bone morphogenetic proteins on neural tissues. In: S Vukicevic, KT Sampath (eds): Bone morphogenetic proteins. From laboratory to clinical practice. Birkhauser Verlag, Basel, Switzerland, 289–321
Dudley AT, Lyons KM, Robertson EJ (1995) A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9: 2795–2807
Graham A, Heyman I, Lumsden A (1993) Even numbered rhombomeres control the apoptotic elimination of neural crest cells from odd-numbered rhombomeres in the chick hindbrain. Development 119: 233–245
Hirsinger E, Jouve C, Malapert P, Pourquie O (1998) Role of growth factors in shaping the developing somite. Mol Cell Endocrin 140: 83–87
Sanz-Ezquerro JJ, Tickle C (2001) “Fingering” the vertebrate limb. Differentiation 69: 91–99
Niswander L (2002) Interplay between the molecular signals that control vertebrate limb development. Int J Dev Biol 46: 877–881
Laufer E, Nelson C, Johnson RL, Morgan BA, Tabin C (1994) Sonic hedgehog and Fgf4 act through a signalling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell 79: 993–1003
Capdevila J, Tsukui T, Rodriquez Esteban C, Zappavigna V, Izpisua Belmonte JC (1999) Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin. Mol Cell 4: 893–849
Merino R, Rodriguez-Leon J, Macias D, Ganan Y, Economides AN, Hurle JM (1999) The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. Development 127: 5515–5522
Dudley AT, Tabin CJ (2000) Constructive antagonism in limb development. Curr Op Gen Develop 10: 387–392
Lyons KM, Hogan BLM, Robertson EJ. (1995) Colocalization of Bmp 7 and Bmp 2 RNAs suggest that these factors cooperatively mediate tissue interactions during murine development. Mech Dev 50: 71–83
Hofmann C, Luo G, Balling R, Karsenty G (1996) Analysis of limb patterning in BMP7 deficient mice. Dev Gen 19: 43–50
Dunn Nr, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BLM (1997) Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and A1x4. Dev Biol 188: 235–247
Kontges G, Lumsden A (1996) Rhombocephalic neural crest segmentation is preserved throughout craniofacial ontogeny. Development 122: 3229–3242
Karsenty G (1998) Genetics of skeletogenesis. Dev Gen 22: 301–313
Reddi AH (1994) Bone and cartilage differentiation. Curr Opin Genet Dev 4: 737–744
Hall BK, Miyake T (1995) Divide, accumulate, differentiate: cell condensation in skeletal development revisited. Int J Dev Biol 39: 881–893
Duprez D, Bell EJdeH, Richardson MK, Archer CW, Wolpert L, Brickell PM, Francis-West PH (1996) Overexpression of BMP-2 and BMP-4 alters the size and shape of developing skeletal elements in the chick limb. Mech Dev 57: 145–157
Urist MR (1965) Bone: formation by autoinduction. Science 150: 893–899
Hall BK, Miyake T (2000) All for one and one for all: condensations and the initiation of skeletal development. BioEssays 22: 138–147
Kingsley DM, Bland AE, Grubber JM, Marker PC, Russel LB, Copeland NG, Jenkins NA (1992) The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell 71: 399–410
Baur ST, Mai JJ, Dymecki SM (2000) Combinatorial signaling through BMP receptor IB and GDFS; shaping of the distal mouse limb and the genetics of distal limb diversity. Development 127: 605–619
Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ (1994) Limb alterations in brachypodism mice due to the mutations in a new member of the TGF13- superfamily. Nature 368: 639–643
Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J, Luyten FP (1996) A human chondrodysplasia due to the mutation in a TGF-I3 superfamily member. Nat Gen 12: 315–318
Thomas JT, Kilpatrick MW, Lin K, Erlacher L, Lembessis P, Costa T, Tsipouras P, Luyten FP (1997) Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nat Gen 17: 58–64
Kronenberg HM (2003) Development regulation of the growth plate. Nature 423: 332–336
Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A (2002) Interaction of FGF, Ihh/PthIh, and BMP signaling integrates chondrocyte proliferation and hypertophic differentiation. Dev Cell 3: 439–449
Macias D, Ganan Y, Sampath TK, Piedra ME, Ros MA, Hurle JM (1997) Role of BMP2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development. Development 124: 1109–1117
Cobourne MT, Sharpe PT (2003) Tooth and jaw: molecular mechanisms of pattering in the first branchial arch. Arch Oral Biol 48: 1–14
Vainio S, Karavanova I, Jowett A, Thesleff I (1993) Identification of Bmp-4 as signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75: 45–58
Vaahtokari A, Aberg T, Thesleff I (1996) Apoptosis in the developing tooth: association with an embryonic signaling center and supression by EGF and FGF. Development 122: 121–129
Naeve B, Holder N, Patient R (1997) A graded response to BMP-4 spatially coordinates patterning of the mesoderm and ectoderm in the zebrafish. Mech Dev 62: 183–195
Cossu G, Borello U (1999) Wnt signalling and the activation of myogenesis in mammals. EMB O J 18: 6867–6872
McPherron AC, Lawler AM, Lee S-J (1997) Regulation of skeletal muscle mass in mice by a new TGF-3 superfamily member. Nature 387: 83–90
Paralkar VM, Grasser WA, Baumann AP, Castleberry TA, Owen TA, Vukicevic S (2002) Prostate-derived factor and growth and differentiation factor-8: newly discovered members of TGF-3 superfamily. In: S Vukicevic, KT Sampath (eds): Bone morphogenetic proteins. From laboratory to clinical practice. Birkhauser Verlag, Basel, Switzerland, 19–31
Lechner MS, Dressler GR (1997) The molecular basis of embryonic kidney development. Mech Dev 62: 105–120
Godin RE, Robertson EJ, Dudley AT (1999) Role of BMP family members during kidney development. Int J Dev Biol 43: 405–411
Vukicevic S, Latin V, Chen P, Batorsky R, Reddi AH, Sampath K (1994) Localization of osteogenic protein-1 (Bone morphogenetic protein 7) during human embryonic development: high affinity binding to basement membranes. Biochem Biophys Res Commun 198: 693–700
Ruppert R, Hoffmann E, Sebald W (1996) Human bone morphogenetic protein 2 contains a heparin binding site which modifies its biological activity. Eur J Biochem 237: 295–302
Luo G, Hofmann C, Bronckers ALJJ, Sohocki M, Bradley A, Karsenty G (1995) Bmp7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 9: 2808–2820
Winnier G, Blessing M, Labosky PA, Hogan BLM (1995) Bone morphogenetic protein4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9: 2105–2116
Zhang H, Bradley A (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122: 2977–2986
Miyazaki Y, Oshima K, Fogo A, Hogan BL, Ichikawa I (2000) Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J Clin Invest 105: 863–873
Piscione TD, Yager TD, Gupta IR, Grinfeld B, Pei Y, Attisano L, Wrana JL, Rosenblum ND (1997) BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis. Am J Physiol 273: 961–975
King JA, Marker PC, Seung KS, Kingsley DM (1994) BMPS and the molecular, skeletal and soft tissue alterations in short ear mice. Dev Biol 166: 112–122
Vukicevic S, Kopp JB, Luyten FP, Sampath TK (1996) Induction of nephrogenic mesenchyme by osteogenic protein 1 (bone morphogenetic protein 7). Proc Natl Acad Sci USA 93: 9021–9026
Dudley AT, Godin RE, Robertson EJ (1999) Interaction between FGF and BMP signalling pathways regulates development of metanephric mesenchyme. Genes Dev 13: 1601–1613
Vukicevic S, Basic V, Rogic D, Basic N, Shih MS, Shepard A, Jin D, Dattatreyamurty B, Jones W, Dorai H et al (1998) Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat. J Clin Invest 102: 202–214
Roberts DJ, Smith DM, Goff DJ, Tabin CJ (1998) Epithelial-mesenchymal signaling during the regionalization of the chick gut. Development 125: 2791–2801
Smith DM; Nielsen C, Tabin CJ, Roberts DJ (2000) Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary. Development 127: 3671–3681
Maric I, Poljak L, Zoricic S, Bobinac D, Bosukonda D, Sampath KT, Vukicevic S (2003) Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats. J Cell Physiol 196: 258–264
Roberts DJ, Johnson RL, Burke AC, Nelson CE, Morgan BA, Tabin CT (1995) Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 121: 3163–3174
Hoffman MP, Kidder BL, Steinberg ZL, Lakhani S, Ho S, Kleinman HK, Larsen M (2002) Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development 129: 5767–5778
Zaret KS (2001) Hepatocyte differentiation: from the endoderm and beyond. Curr Opin Gen Develop 11: 568–574
Furuta Y, Piston DW, Hogan BL (1977) Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124: 2203–2212
Miller AF, Harvey SA, Thies RS, Olson MS (2000) Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver. J Biol Chem 275: 17937–17945
Dichmann DS, Miller CP, Jensen J, Scott Heller R, Serup P (2003) Expression and misexpression of members of the FGF and TGFI3 families of growth factors in the developing mouse embryos. Dev Dyn 226: 663–674
Miralles F, Czernichow P, Ozaki K, Itah N, Scharfmann R (1999) Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas. Proc Nat! Acad Sci USA 96: 6267–6272
Warburton D, Schwarz M, Tefft D, Flores-Delgado G, Anderson KD, Cardoso WV (2000) The molecular basis of lung morphogenesis. Mech Dev 92: 55–81
Lu MM, Yang H, Zhang L, Shu W, Blair DG, Morrisey EE (2001) The bone morphogenetic protein antagonist gremlin regulates proximal-distal patterning of the lung. Dev Dyn 222: 667–680
Vukicevic S, Helder MN, Luyten FP (1994) Developing human lung and kidney are major sites for synthesis of bone morphogenetic protein-3 (osteogenin). J Histochem Cytochem 42: 869–875
Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan BLM (1996) Evidence from normal expression and targeted misexpression that bone morphogenetic protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development 122: 1693–1702
Weaver M, Yingling JM, Dunn NR, Bellusci S, Hogan BLM (1999) Bmp signalling regulates proximal-distal differentiation of endoderm in mouse lung development. Development 126: 4005–4015
Weaver M, Dunn NR, Hogan BLM (2000) Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 127: 2695–2704
Schneider MD, Gaussin V, Lyons KM (2003) Tempting fate: BMP signals for cardiac morphogenesis. Cytokine Growth Fact Rev 14: 1–4
Walters MJ, Wayman GA, Christian JL (2001) Bone morphogenetic function is required for terminal differentiation of the heart but not for early expression of cardiac marker genes. Mech Dev 100: 263–273
Kim RY, Robertson EJ, Solloway MJ (2001) Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol 235: 449–466
Solloway MJ, Robertson EJ (1999) Early embryonic lethality in BmpS Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development 126: 1753–1768
Olson EN (2001) The path to the heart and the road not taken. Science 291: 2327–2328
Solloway MJ, Harvey RP (2003) Molecular pathways in myocardial development: a stem cell perspective. Cardiovasc Res 58: 264–277
Schultheiss TM, Burch JB, Lassar AB (1997) A role of bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 11: 451–462
Andree B, Duprez D, Vorbusch B, Arnold HH, Brand T (1998) BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos. Mech Dev 70: 119–131
Monzen K, Nagai R, Komuro I (2002) A role for bone morphogenetic protein signalling in cardiomyocyte differentiation. Trends Cardiovasc Med 12: 263–269
Marvin MJ, Di Rocco G, Gardiner A, Bush SM, Lassar AB (2001) Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev 15: 316–327
Schneider VA, Mercola M (2001) Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev 15: 304–315
Breckenridge RA, Mohun TJ, Amaya E (2001) A role for BMP signalling in heart looping morphogenesis in Xenopus. Dev Biol 232: 191–203
Nakajima Y, Yamagishi T, Hokari S, Nakamura H (2000) Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-I3 and bone morphogenetic protein (BMP). Anat Rec 258: 119–127
Delot EC (2003) Control of endocardial cushion and cardiac valve maturation by BMP signalling pathways. Mol Gen Met 80: 27–35
Baron MH (2001) Induction of embryonic hematopoietic and endothelial stem/progenitor cells by hedgehog-mediated signals. Differentiation 68: 175–185
Baron MH (2003) Embryonic origins of mammalian hematopoiesis. Exp Hemat 31: 1160–1169
Martinovic S, Mazic S, Kisic V, Basic N, Jakic-Razumovici J, Borovecki F, Batinic D, Simic P, Grgurevic L, Labar B et al (2004) Expression of bone morphogenetic proteins in stromal cells from human bone marrow long-term culture. J Histochem Cytochem; in press
Findlay JK, Drummond AE, Dyson ML, Baillie AJ, Robertson DM, Ethier JF (2002) Recruitment and development of the follicle; the roles of the transforming growth factor-13 superfamily. Mol Cell Endocrin 191: 35–43
Ying Y, Qi X, Zhao GQ (2001) Induction of primordial germ cells from murine epiblast by synergistic action of BMP4 and BMP8B signalling pathways. Proc Natl Acad Sci USA 98: 7858–7862
Shimasaki S, Zachow RJ, Li DM, Kim H, Iemura S, Ueno N, Sampath K, Chang RJ, Erickson GF (1999) A functional bone morphogenetic protein system in the ovary. Proc Natl Acad Sci USA 96: 7282–7287
Dong J, Albertini D, Nishimori K, Lu N, Matzuk M (1996) Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383: 531–535
Galloway SM, McNatty KP, Cambridge LM, Laitinen MPE, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW et al (2000) Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature 25: 279–283
Solloway MJ, Dudley AT, Bikoff EK, Lyons KM, Hogan BLM, Robertson EJ (1998) Mice lacking Bmp6 function. Dev Gen 22: 321–339
Knight PG, Glister C (2001) Potential local regulatory functions of inhibins, activins and follistatin in the ovary. Reproduction 121: 503–512
Durlinger AL, Kramer P, Karels B, de Jong FG, Uilenbroek JT, Grootegoed JA, Them-men AP (1999) Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140: 5789–5796
Martinovic S, Latin V, Suchanek E, Stavljenic-Rukavina A, Sampath KI, Vukicevic S. (1996) Osteogenic protein-1 is produced by human fetal trophoblasts in vivo and regulates the synthesis of chorionic gonadotropin and progesterone by trophoblasts in vitro. Eur J Clin Chem Clin Biochem 34: 103–109
Ozkaynak E, Jin DF, Jelic M, Vukicevic S, Oppermann (1997) Osteogenic protein-1 mRNA in the uterine endometrium. Biochem Biophys Res Commun 234: 242–246
Zhao GQ, Liaw L, Hogan BLM (1998) Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of epididymis. Development 125: 1103–1112
Wilson PA, Hemmati-Brivanlou A (1995) Induction of epidermis and inhibition of neural fate by BMP-4. Nature 376: 331–333
Botchkarev VA (2003) Bone morphogenetic proteins and their antagonists in skin and hair follicle biology. J Invest Dermatol 120: 36–47
Lyons KM, Peltron RW, Hogan BL (1989) Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-beta-like genes coordinately regulate aspects of embryonic development. Genes Dev 3: 1657–1668
Takahashi H, Ikeda T (1996) Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos. Dev Dyn 207: 439–449
Blessing M, Schirmacher P, Kaiser S (1996) Overexpression of bone morphogenetic pro-tein-6 in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions. J Cell Biol 135: 227–239
Botchkarev VA, Botchkareva NV, Roth W, Nakamura M, Chen LH, Herzog W, Lindner G, McMahon JA, Peters C, Lauster R et al (1999) Noggin is mesenchymally-derived stimulator of hair follicle induction. Nature Cell Biol 1: 158–164
Jung HS, Francis West PH, Widelitz RB (1998) Local inhibitory action of BMP and their relationship with activators in feather formation: implications for periodic patterning. Dev Biol 196: 11–23
Noramly S, Morgan BA (1998) BMPs mediate lateral inhibition at successive stages in feather tract development. Development 125: 3775–3787
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Simic, P., Vukicevic, S. (2004). Bone morphogenetic proteins in development. In: Vukicevic, S., Sampath, K.T. (eds) Bone Morphogenetic Proteins: Regeneration of Bone and Beyond. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7857-9_4
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