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The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis

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Summary

Elements of the vertebrate skeleton are initiated as cell condensations, collectively termed the ‘membranous skeleton’ whether cartilages or bones by Grüneberg (1963). Condensations, which were identified as the basic cellular units in a recent model of morphological change in development and evolution (Atchley and Hall 1991) are reviewed in this paper. Condensations are initiated either by increased mitotic activity or by aggregation of cells towards a centre. Prechondrogenic (limb bud) and preosteogenic (scierai ossicle) condensations are discussed and contrasted. Both types of skeletogenic condensations arise following epithelial-mesenchymal interactions; condensations are identified as the first cellular product of such tissue interactions. Molecular characteristics of condensations are discussed, including peanut agglutinin lectin, which is used to visualize prechondrogenic condensations, and hyaluronan, hyaladherins, heparan sulphate proteoglycan, chondroitin sulphate proteoglycan, versican, tenascin, syndecan, N-CAM, alkaline phosphatase, retinoic acid and homeobox-containing genes. The importance for the initiation of chondrogenesis or osteogenesis of upper and lower limits to condensation size and the numbers of cells in a condensation are discussed, as illustrated by in vitro studies and by mutant embryos, including Talpid3 in the chick and Brachypod, Congenital hydrocephalus and Phocomelia in the mouse. Evidence that genes specific to the skeletal type are selectively activated at condensation is discussed, as is a recent model involving TGF-β and fibronectin in condensation formation. Condensations emerge as a pivotal stage in initiation of the vertebrate skeleton in embryonic development and in the modification of skeletal morphology during evolution.

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References

  • Abbott LA, Lester SM, Erickson CA (1991) Changes in mesenchymal cell-shape, matrix collagen and tenascin accompany bud formation in the embryonic chick lung. Anat Embryol 183:299–311

    Google Scholar 

  • Ahrens PB, Solursh M, Reiter RS (1977) Stage-related capacity for limb chondrogenesis in cell culture. Dev Biol 60:69–82

    Google Scholar 

  • Alberch P, Gould SJ, Oster GF, Wake DB (1979) Size and shape in ontogeny and phytogeny. Paleobiology 5:296–317

    Google Scholar 

  • Atchley WR, Fitch WM (1991) Gene trees and the origins of inbred strains of mice. Science 254:554–558

    Google Scholar 

  • Atchley WR, Hall BK (1991) A model for development and evolution of complex morphological structures. Biol Rev 66:101–157

    Google Scholar 

  • Aulthouse AL, Solursh M (1987) The detection of a precartilage, blastema-specific marker. Dev Biol 120:377–384

    Google Scholar 

  • Bagnall KM, Sanders EJ (1989) The binding pattern of peanut lectin associated with sclerotome migration and the formation of the vertebral axis in the chick embryo. Anat Embryol 180:505–513

    Google Scholar 

  • Banerjee SD, Toole BP (1990) Monoclonal antibody to chick embryo hyaluran-binding protein: changes in distribution of binding of protein during early brain development. Dev Biol 146:186–197

    Google Scholar 

  • Bard JBL (1990) Traction and the formation of mesenchymal condensations in vivo. Bioessays 12:389–395

    Google Scholar 

  • Bee JA, von der Mark K (1990) An analysis of chick limb bud intercellular adhesion underlying the establishment of cartilage aggregates in suspension culture. J Cell Sci 96:527–536

    Google Scholar 

  • Breen M, Richardson R, Bondareff W, Weinstein HG (1973) Acid glycosaminoglycans in developing sternocostal cartilage of the hydrocephalic ch/ch mouse. Biochim Biophys Acta 304:828–836

    Google Scholar 

  • Castagnola P, Dozin B, Moro G, Cancedda R (1988) Changes in the expression of collagen genes show two stages in chondrocyte differentiation in vitro. J Cell Biol 106:461–468

    Google Scholar 

  • Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47:131–139

    Google Scholar 

  • Chuong C-M, Edelman GM (1985) Expression of cell-adhesion molecules in embryonic induction. I. Morphogenesis of nestling feathers. J Cell Biol 101:1009–1026

    Google Scholar 

  • Coelho CND, Kosher RA (1991) Gap junctional communication during limb cartilage differentiation. Dev Biol 144:47–53

    Google Scholar 

  • Cottrill CP, Archer CW, Wolpert L (1987) Cell sorting and chondrogenic aggregate formation in micromass culture. Dev Biol 122:503–515

    Google Scholar 

  • Coulombre AJ, Coulombre JL, Mehta H (1962) The skeleton of the eye. I. Conjunctival papillae and scleral ossicles. Dev Biol 5:382–401

    Google Scholar 

  • D'Amico-Martel A, van de Water TR, Wooton JAM, Minor RR (1987) Changes in the types of collagen synthesized during chondrogenesis of the mouse otic capsule. Dev Biol 120:542–555

    Google Scholar 

  • Doty SB, Schofield BH (1990) Histochemistry and enzymology of bone forming cells. In: Hall BK (ed) Bone, vol 1. The osteoblast and osteocyte. Telford Press, Caldwell New Jersey, pp 71–102

    Google Scholar 

  • Duke JC (1983) Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity. Teratology 27:427–436

    Google Scholar 

  • Duke J, Elmer WA (1977) Effect of brachypod mutation on cell adhesion and chondrogenesis in aggregates of mouse limb mesenchyme. J Embryol Exp Morphol 42:209–217

    Google Scholar 

  • Duke J, Elmer WA (1978) Cell adhesion and chondrogenesis in brachypod mouse limb mesenchyme: fragment fusion studies. J Embryol Exp Morphol 48:161–168

    Google Scholar 

  • Ede DA (1971) Control of form and pattern in the vertebrate limb. Symp Soc Exp Biol 25:235–254

    Google Scholar 

  • Ede DA (1983) Cellular condensations and chondrogenesis. In: Hall BK (ed) Cartilage, vol 2. Development, differentiation and growth. Academic Press, New York, pp 143–185

    Google Scholar 

  • Ede DA, Agerback GS (1968) Cell adhesion and movement in relation to the developing limb pattern in normal and talpid3 mutant chick embryos. J Embryol Exp Morphol 20:81–100

    Google Scholar 

  • Ede DA, Flint OP (1972) Patterns of cell division, cell death ad chondrogenesis in cultured aggregates of normal and talpid3 mutant chick limb mesenchyme cells. J Embryol Exp Morphol 27:245–260

    Google Scholar 

  • Ede DA, Flint OP (1975 a) Intercellular adhesion and formation of aggregates in normal and talpid3 mutant chick limb mesenchyme. J Cell Sci 18:97–112

    Google Scholar 

  • Ede DA, Flint OP (1975b) Cell movement and adhesion in the developing chick wing bud: studies on cultured mesenchyme cells from normal and talpid3 mutant embryos. J Cell Sci 18:301–314

    Google Scholar 

  • Ede DA, Kelley WA (1964a) Developmental abnormalities in the head region of the talpid3 mutant of the fowl. J Embryol Exp Morphol 12:161–182

    Google Scholar 

  • Ede DA, Kelley WA (1964b) Developmental abnormalities in the trunk and limbs of the talpid3 mutant of the fowl. J Embryol Exp Morphol 12:339–356

    Google Scholar 

  • Ede DA, Hinchliffe JR, Mees HC (1971) Feather morphogenesis and feather pattern in normal and talpid3 mutant chick embryos. J Embryol Exp Morphol 25:65–83

    Google Scholar 

  • Ede DA, Flint OP, Wilby OK, Colquhoun P (1977) The development of pre-cartilage condensations in limb bud mesenchyme in vivo and in vitro. Br Soc Dev Biol Symp 3:161–179

    Google Scholar 

  • Edelman GM (1986) Cell adhesion molecules in the regulation of animal form and tissue pattern. Ann Rev Cell Biol 2:81–116

    Google Scholar 

  • Edelman GM (1988) Topobiology: An introduction to molecular embryology. Basic Books, New York

    Google Scholar 

  • Elmer WA (1977) Morphological and biochemical modifications of cartilage differentiation in the brachypod and other micromelic mouse embryos. Colloq Int CNRS 266:235–242

    Google Scholar 

  • Elmer WA, Selleck DK (1975) In vitro chondrogenesis of limb mesoderm from normal and brachypod mouse embryos. J Embryol Exp Morphol 33:371–386

    Google Scholar 

  • Elmer WA, Pennypacker MF, Knudsen TB, Kwasigroch TE (1988) Alterations in cell surface galactosyltransferase activity during limb chondrogenesis in brachypod mutant mouse embryos. Teratology 38:475–484

    Google Scholar 

  • Epperlein HH, Lehmann R (1975) Ectomesenchymal-endodermal interaction system (EEIS) of Triturus alpestris in tissue culture. 2. Observations on differentiation of visceral cartilage. Differentiation 4:159–174

    Google Scholar 

  • Erickson HP, Bourdon MA (1989) Tenascin: an extracellular matrix protein prominent in specialized embryonic tissues and tumors. Ann Rev Cell Biol 5:71–92

    Google Scholar 

  • Fell HB (1925) The histogenesis of cartilage and bone in the long bones of the embryonic fowl. J Morphol Physiol 40:417–459

    Google Scholar 

  • Fell HB, Canti GR (1934) Experiments on the development in vitro of the avian knee-joint. Proc R Soc Lond [Biol] 116:316–351

    Google Scholar 

  • Fitch N (1957) An embryological analysis of two mutants in the mouse, both producing cleft palates. J Exp Zool 136:329–357

    Google Scholar 

  • Flanders KC, Thompson NL, Cissel DS, van Obberghen-Schilling E, Baker CC, Kass ME, Ellingsworth LR, Roberts AB, Sporn MB (1989) Transforming growth factor-β1:histochemical localization with antibodies to different epitopes. J Cell Biol 108:653–660

    Google Scholar 

  • Flickinger RA (1974) Muscle and cartilage differentiation in small and large expiants from the chick limb bud. Dev Biol 41:202–208

    Google Scholar 

  • Flint OP, Ede DA, Wilby OK, Proctor J (1978) Control of somite number in normal and amputated mutant mouse embryos: an experimental and a theoretical analysis. J Embryol Exp Morphol 45:189–202

    Google Scholar 

  • Frenz DA, Jaikaria NS, Newman SA (1989) The mechanism of precartilage mesenchymal condensation: a major role for interaction of the cell surface with the amino-terminal heparin-binding domain of fibronectin. Dev Biol 136:97–103

    Google Scholar 

  • Fyfe DM, Hall BK (1981) A scanning electron microscopic study of the developing epithelial scleral papillae in the eye of the embryonic chick. J Morphol 167:201–209

    Google Scholar 

  • Fyfe DM, Hall BK (1983) The origin of the ectomesenchymal condensations which precede the development of the bony scleral ossicles in the eyes of embryonic chicks. J Embryol Exp Morphol 73:69–86

    Google Scholar 

  • Gallagher JT (1989) The extended family of proteoglycans: social residents of the pericellular zone. Curr Opin Cell Biol 1:1201–1218

    Google Scholar 

  • Gearhart JD, Mintz B (1972) Clonal origins of somites and their muscle derivatives: evidence from allophenic mice. Dev Biol 29:27–37

    Google Scholar 

  • Gluecksohn-Waelsch S, Hagedorn D, Sisken BF (1956) Genetics and morphology of a recessive mutation in the house mouse affecting head and limb skeleton. J Morphol 99:465–479

    Google Scholar 

  • Godman GC, Porter KR (1960) Chondrogenesis studied with the electron microscope. J Biophys Biochem Cytol 5:221–255

    Google Scholar 

  • Goldspink DF (1980) Development and specialization of skeletal muscle. Cambridge University Press, Cambridge

    Google Scholar 

  • Götz W, Fischer G, Herken R (1991) Lectin binding pattern in the embryonal and early fetal human vertebral column. Anat Embryol 184:345–353

    Google Scholar 

  • Gould RP, Day A, Wolpert L (1972) Mesenchymal condensations and cell contact in early morphogenesis of the chick limb. Exp Cell Res 72:325–336

    Google Scholar 

  • Gould RP, Selwood L, Day A, Wolpert L (1974) The mechanism of cellular orientation during early cartilage formation in the chick limb and regenerating amphibian limb. Exp Cell Res 83:287–296

    Google Scholar 

  • Green MC (1970) The developmental effects of congenital hydrocephalus (ch) in the mouse. Dev Biol 23:585–608

    Google Scholar 

  • Grüneberg H (1943) Congenital hydrocephalus in the mouse, a case of spurious pleiotropism. J Genet 45:1–21

    Google Scholar 

  • Grüneberg H (1953) Genetical studies on the skeleton of the mouse. VII. Congenital hydrocephalus. J Genet 51:327–358

    Google Scholar 

  • Grüeberg H (1963) The pathology of development: a study of inherited skeletal disorders in animals. Blackwell, Oxford

    Google Scholar 

  • Grüneberg H, Lee AJ (1973) The anatomy and development of brachypodism in the mouse. J Embryol Exp Morphol 30:119–141

    Google Scholar 

  • Grüneberg H, Wickramaratne GAde S (1974) A re-examination of two skeletal mutants of the mouse, vestigal tail (vt) and congenital hydrocephalus (ch). J Embryol Exp Morphol 31:207–222

    Google Scholar 

  • Hale LJ (1956a) Mitotic activity during the early skeletal differentiation of the scleral bones in the chick. Q J Microsc Sci 97:333–353

    Google Scholar 

  • Hale LJ (1956b) Mesodermal cell deaths during the early development of the scleral bones in the chick. Q J Microsc Sci 97:355–368

    Google Scholar 

  • Hall BK (1968) Histochemical aspects of the differentiation of adventitious cartilage on the membrane bones of the embryo chick. Histochemie 16:206–220

    Google Scholar 

  • Hall BK (1970) Cellular differentiation in skeletal tissues. Biol Rev 45:455–484

    Google Scholar 

  • Hall BK (1978) Developmental and cellular skeletal biology. Academic Press, New York

    Google Scholar 

  • Hall BK (1981) Specificity in the differentiation and morphogenesis of neural crest-derived scleral ossicles and of epithelial scleral papillae in the eye of the embryonic chick. J Embryol Exp Morphol 66:175–190

    CAS  Google Scholar 

  • Hall BK (1982a) How is mandibular growth controlled during development and evolution? J Craniofac Genet Dev Biol 2:45–49

    Google Scholar 

  • Hall BK (1982b) Mandibular morphogenesis and craniofacial malformations. J Craniofac Genet Dev Biol 2:309–322

    Google Scholar 

  • Hall BK (1982c) The role of tissue interactions in the growth of bone. In: Dixon AD, Sarnat BG (eds) Factors and mechanisms influencing bone growth. Liss, New York, pp 205–215

    Google Scholar 

  • Hall BK (1983) Cartilage, vol 2. Development, differentiation and growth. Academic Press, New York

    Google Scholar 

  • Hall BK (1984a) Developmental processes and heterochrony as an evolutionary mechanism. Can J Zool 62:1–7

    CAS  PubMed  Google Scholar 

  • Hall BK (1984b) Developmental mechanisms underlying the formation of atavisms. Biol Rev 59:89–124

    Google Scholar 

  • Hall BK (1988) The embryonic development of bone. Am Sci 76:174–181

    Google Scholar 

  • Hall BK (1990) Heterochronic change in vertebrate development. Semin Dev Biol 1:237–243

    Google Scholar 

  • Hall BK (1992a) Evolutionary developmental biology. Chapman & Hall, London

    Google Scholar 

  • Hall BK (1992b) Cell-cell interactions in craniofacial growth and development. In: Davidovitch Z (ed) Biological mechanisms of tooth movement and craniofacial adaptation. EBSCO Media, Birmingham, AL, pp 261–267

    Google Scholar 

  • Hall BK, Coffin-Collins PA (1990) Reciprocal interactions between epithelium, mesenchyme, and epidermal growth factor (EGF) in the regulation of mandibular mitotic activity in the embryonic chick. J Cranofac Genet Dev Biol 10:241–261

    CAS  Google Scholar 

  • Hall BK, Ekanayake S (1991) Effects of growth factors on the differentiation of neural crest cells and neural crest-cell derivatives. Int J Dev Biol 35:367–386

    Google Scholar 

  • Harris AK, Stopak D, Wild P (1980a) Fibroblast traction as a mechanism for collagen morphogenesis. Nature 290:249–251

    Google Scholar 

  • Harris AK, Wild P, Stopak D (1980b) Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208:177–179

    Google Scholar 

  • Harris AK, Stopak D, Warner P (1984) Generation of spatially periodic patterns by a mechanical instability; a mechanical alternative to the Turing model. J Embryol Exp Morphol 80:1–20

    Google Scholar 

  • Heine UI, Munoz EF, Flanders KC, Ellingsworth LR, Lam H-Y P, Thompson NL, Roberts AB, Sporn MB (1987) The role of transforming growth factor-β in the developing mouse embryo. J Cell Biol 105:2861–2876

    Google Scholar 

  • Hewitt AT, Elmer WA (1976) Reactivity of normal and brachypod mouse limb mesenchyme cells with ConA. Nature 264:177–178

    Google Scholar 

  • Hewitt AT, Elmer WA (1978) The involvements of microfilaments and microtubules in the lateral mobility of lectin binding sites of normal and brachypod mouse limb mesenchyme. Cell Differ 7:295–303

    Google Scholar 

  • Hinchliffe JR (1989) Reconstructing the Archetype: innovation and conservatism in the evolution and development of the pentadactyl limb. In: Wake DB, Roth G (eds) Complex organismal function: integration and evolution in vertebrates. Wiley, New York, pp 171–189

    Google Scholar 

  • Hinchliffe JR, Ede DA (1967) Limb development in the polydactylous talpid3 mutant of the fowl. J Embryol Exp Morphol 17:385–404

    Google Scholar 

  • Hinchliffe JR, Ede DA (1968) Abnormalities in bone and cartilage development in the talpid3 mutant of the fowl. J Embryol Exp Morphol 19:327–339

    Google Scholar 

  • Hinchliffe JR, Johnson DR (1980) The development of the vertebrate limb. Oxford University Press, London

    Google Scholar 

  • Hinchliffe JR, Thorogood PV (1974) Genetic inhibition of mesenchymal cell death and the development of form and skeletal pattern in the limbs of talpid3 (ta3) mutant chick embryos. J Embryol Exp Morphol 31:747–760

    Google Scholar 

  • Holtfreter J (1968) Mesenchyme and epithelia in inductive and morphogenetic processes. In: Feischmajer P, Billingham RE (eds) Epithelial-mesenchymal interactions. Williams & Wilkins, Baltimore, pp 1–30

    Google Scholar 

  • Hurle JM, Ganan Y (1986) Interdigital tissue chondrogenesis induced by surgical removal of the ectoderm in the embryonic chick leg bud. J Embryol Exp Morphol 94:231–244

    Google Scholar 

  • Hurle JM, Ros MA, Hinchliffe JR (1988) Spatial and temporal changes in the pattern of glycosylation of the developing chick limb tissue components as revealed by fluorescent conjugated lectin probes. Cell Differ Dev 24:149–158

    Google Scholar 

  • Hurle JM, Hinchliffe JR, Ros MA, Citchlow MA, Genis-Galvez JM (1989a) The extracellular matrix architecture relating to myotendinous pattern formation in the distal part of the developing chick limb: an ultrastructural, histochemical and immunocytochemical analysis. Cell Differ Dev 27:103–120

    Google Scholar 

  • Hurle JM, Ganan Y, Marcias D (1989b) Experimental analysis of the in vivo chondrogenic potential of the interdigital mesenchyme of the chick leg bud subjected to local ectodermal removal. Dev Biol 132:368–374

    Google Scholar 

  • Jacobson W, Fell HB (1941) The developmental mechanics and potencies of the undifferentiated mesenchyme of the mandible. Q J Microsc Sci 82:563–586

    Google Scholar 

  • Janners MY, Searls RL (1970) Changes in rate of cellular proliferation during the differentiation of cartilage and muscle in mesenchyme of the embryonic chick wing. Dev Biol 23:136–165

    Google Scholar 

  • Johnson LG (1973) Development of chick embryo conjunctival papillae and scleral ossicles after hydrocortisone treatment. Dev Biol 30:223–227

    Google Scholar 

  • Johnson DR (1986) The genetics of the skeleton. Clarendon Press, Oxford

    Google Scholar 

  • Jones CM, Lyons KM, Hogan BLM (1991) Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111:531–542

    CAS  PubMed  Google Scholar 

  • Jurand A (1965) Ultrastructural aspects of early development of the fore-limb buds in the chick and mouse. Proc R Soc Lond [Biol] 162:387–405

    Google Scholar 

  • Katz MJ (1980) Allometry formula: a cellular model. Growth 44:89–96

    Google Scholar 

  • Katz MJ, Lasek RJ (1978) Evolution of the nervous system: role of ontogenetic mechanisms in the evolution of matching populations. Proc Natl Acad Sci USA 75:1349–1352

    Google Scholar 

  • Kelley RO, Fallon JF (1978) Identification and distribution of gap junctions in the mesoderm of the developing chick limb bud. J Embryol Exp Morphol 46:99–110

    Google Scholar 

  • Kelley RO, Fallon JF (1983) A freeze-fracture and morphometric analysis of gap junctions of limb bud cells: initial studies on a possible mechanism for morphogenetic signalling during development. In: Fallon JF, Caplan AI (eds) Limb development and regeneration. Part A, Liss, New York, pp 119–130

    Google Scholar 

  • Knudson CB, Toole BP (1985) Changes in the pericellular matrix during differentiation of limb bud mesoderm. Dev Biol 112:308–318

    Google Scholar 

  • Knudson CB, Toole BP (1987) Hyaluronate-cell interactions during differentiation of chick embryo limb mesoderm. Dev Biol 124:82–90

    Google Scholar 

  • Kochhar DM (1973) Limb development in mouse embryos. 1. Analysis of teratogenic effects of retinoic acid. Teratology 7:289–295

    Google Scholar 

  • Kosher RA (1983) The chondroblast and the chondrocyte. In: Hall BK (ed) Cartilage, vol 1. Structure, function and biochemistry. Academic Press, New York, pp 59–85

    Google Scholar 

  • Kosher RA, Kulyk WM, Gay SW (1986a) Collagen gene expression during limb cartilage differentiation. J Cell Biol 102:1151–1156

    Google Scholar 

  • Kosher RA, Gay SW, Kamanitz JR, Kulyk WM, Rodgers BJ, Sai S, Tanaka T, Tanzer M (1986b) Cartilage proteoglycan core protein gene expression during limb cartilage differentiation. Dev Biol 118:112–117

    Google Scholar 

  • Kravis D, Upholt WB (1985) Quantitation of type II procollagen mRNA levels during chick limb cartilage differentiation. Dev Biol 108:164–172

    Google Scholar 

  • Krotoski DM, Elmer WA (1973) Alkaline phosphatase activity in fetal hind limbs of the mouse mutation brachypodism. Teratology 7:99–106

    Google Scholar 

  • Kulyk WM, Rodgers BJ, Greer K, Kosher RA (1989a) Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-β. Dev Biol 135:424–430

    Google Scholar 

  • Kulyk WM, Upholt WB, Kosher RA (1989b) Fibronectin gene expression during limb cartilage differentiation. Development 106:449–455

    Google Scholar 

  • Kulyk WM, Coelho CND, Kosher RA (1991) Type-IX collagengene expression during limb cartilage differentiation. Matrix 11:282–288

    Google Scholar 

  • Leonard CM, Fuld HM, Frenz DA, Downie SA, Massagué J, Newman SA (1991) Role of transforming growth factor-β in chondrogenic pattern formation in the embryonic limb: stimulation of mesenchymal condensation and fibronectin gene expresssion by exogenous TGF-β and evidence for endogenous TGF-β-like activity. Dev Biol 145:99–109

    Google Scholar 

  • Lewis J, Summerbell D, Wolpert L (1972) Chimaeras and cell lineage in development. Nature 239:276–279

    Google Scholar 

  • Lumsden AGS (1988) Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ. Development 103 [Suppl] 155–169

    Google Scholar 

  • Mackie EJ, Thesleff I, Chiquet-Ehrismann R (1987) Tenascin is associated with chondrogenic differentiation in vivo and promotes chondrogenesis in vitro. J Cell Biol 105:2569–2580

    Google Scholar 

  • Mackie EJ, Tucker RP, Halfter W, Chiquet-Ehrismann R, Epperlein HH (1988) The distribution of tenascin coincides with pathways of neural crest cell migration. Development 102:237–250

    CAS  PubMed  Google Scholar 

  • Maclean N, Hall BK (1987) Cell commitment and differentiation. Cambridge University Press, Cambridge

    Google Scholar 

  • Mallein-Gerin F, Kosher RA, Upholt WB, Tanzer ML (1988) Temporal and spatial analysis of cartilage proteoglycan core protein gene expression during limb development by in situ hybridization. Dev Biol 126:337–345

    Google Scholar 

  • Mark MP, Butler WT, Ruch J-V (1989) Transient expression of a chondroitin sulfate-related epitope during cartilage histomorphogenesis in the axial skeleton of fetal rats. Dev Biol 133:475–488

    Google Scholar 

  • Matsui F, Oohira A, Shoji R, Nogami H (1989) Three distinct molecular species of proteoglycan synthesized by the rat limb bud at the prechondrogenic stage. Arch Biochem Biophys 275:192–201

    Google Scholar 

  • McAleese SR, Sawyer RH (1982a) Avian scale development. IX. Scale formation by scaleless (sc/sc) epidermis under the influence of normal scale dermis. Dev Biol 89:493–502

    Google Scholar 

  • McAleese SR, Sawyer RH (1982b) Correcting the phenotype of the epidermis from chick embryos homozygous for the gene scaleless (sc/sc). Science 214:1033–1034

    Google Scholar 

  • McLaren A (1972) Numerology of development. Nature 239:274–276

    Google Scholar 

  • Mendelsohn C, Ruberte E, Le Meur M, Morriss-Kay G, Chambon P (1991) Developmental analysis of the retinoic acid-insoluble RAR-β2 promoter in transgenic animals. Development 113:723–734

    Google Scholar 

  • Merker HJ, Pospisil M, Mewes P (1975) Cytotoxic effects of 6-mercaptopurine on the limb-bud blastemal cells of rat embryos. Teratology 11:199–218

    Google Scholar 

  • Milaire J (1965a) Étude morphogénétique de trois malformations congénitales de l'autopode chez la souris (syndactylisme-brachypodisme-hémimélie dominante) par des methods cytochimiques. Mém Acad R Belg Sci, Collection in 4° Ser. 16

  • Milaire J (1965b) Aspects of limb morphogenesis in mammals. In: DeHaan EL, Ursprung H (eds) Organogenesis. Holt, Rinehart and Winston, New York, pp 283–300

    Google Scholar 

  • Milaire J (1974) Histochemical aspects of organogenesis in vertebrates. Handbuch der Histochemie [Suppl 3]

  • Milaire J (1978) Étude morphologique, histochemique et autoradiographique du développement du squelette des membres chez l'embryon de Souria. 1. Membres antérieurs. Arch Biol 89:169–216

    Google Scholar 

  • Milaire J (1991) Lectin binding sites in developing mouse limb buds. Anat Embryol 184:479–488

    Google Scholar 

  • Mintz B (1971) Allophenic mice of multi-embryo orign. In: Daniel J, Jr (ed) Methods in Mammalian Embryology. Freeman, San Francisco, pp 186–214

    Google Scholar 

  • Mintz B (1972) Clonal units of gene control in mammalian differentiation. In: Harris R, Allin P, Viza D (eds) Cell Differentiation. Munksgaard, Copenhagen, pp 267–271

    Google Scholar 

  • Mohammed MBH (1989) Cell generation times in normal and Talpid3 mutant chick limb mesenchyme. Folia Morphol 37:435–442

    Google Scholar 

  • Moore WJ, Mintz B (1972) Clonal model of vertebral column and skull development derived from genetically mosaic skeletons of allophenic mice. Dev Biol 27:55–70

    Google Scholar 

  • Müller GB (1989) Developmental mechanisms at the origin of morphological novelty: a side-effect hypothesis. In: Nitecki MH, Nitecki DV (eds) Evolutionary innovations. University of Chicago Press, Chicago, pp 99–130

    Google Scholar 

  • Müller GB, Alberch P (1990) Ontogeny of the limb skeleton in Alligator mississippensis: developmental invariance and change in the evolution of Archosaur limbs. J Morphol 203:151–164

    Google Scholar 

  • Murray PDF (1941) Epidermal papillae and dermal bones of the chick sclerotic. Nature 148:471

    Google Scholar 

  • Murray PDF (1943) The development of the conjunctival papillae and of the scleral bones in the chick embryo. J Anat 77:225–240

    Google Scholar 

  • Nakahara H, Dennis JE, Bruder SP, Haynesworth SE, Lennon DP, Caplan AI (1991) In vitro differentiation of bone and hypertrophic cartilage from periosteal-derived cells. Exp Cell Res 195:492–503

    Google Scholar 

  • Nathanson MA (1989) Differentiation of musculoskeletal tissue. Int Rev Cytol 116:89–164

    Google Scholar 

  • Newman SA (1988) Lineage and pattern in the developing vertebrate limb. Trends Genet 4:329–332

    Google Scholar 

  • Newman SA, Comper WD (1990) ‘Generic’c physical mechanisms of morphogenesis and pattern formation. Development 110:1–18

    Google Scholar 

  • Newman SA, Frenz DA, Tomasek JJ, Paulson DF (1986) Matrixdriven translocation: possible role in precartilage mesenchymal condensation. Prog Clin Biol Res 217B: 199–202

    Google Scholar 

  • Oakley RA, Tosney KW (1991) Peanut agglutin and chondroitin-6-sulfate are molecular markers for tissues that act as barriers to axon advance in the avian embryo. Dev Biol 147:187–206

    Google Scholar 

  • Oster GF, Murray JD (1989) Pattern formation models and developmental constraints. J Exp Zool 251:186–202

    Google Scholar 

  • Oster GF, Shubin N, Murray JD, Alberch P (1988) Evolution and morphogenetic rules: the shape of the vertebrate limb in ontogeny and phylogeny. Evolution 42:862–884

    Google Scholar 

  • Owens EM, Solursh M (1982) Cell-cell interactions by mouse limb cells during in vitro chondrogenesis: analysis of the brachypod mutation. Dev Biol 91:376–388

    Google Scholar 

  • Owens EM, Solursh M (1983) Accelerated maturation of limb mesenchyme by the brachypodH mouse mutation. Differentiation 24:145–148

    Google Scholar 

  • Palmoski M, Goetinck PF (1970) An analysis of the development of conjunctival papillae and scleral ossicles in the eye of the scaleless mutant. J Exp Zool 174:157–164

    Google Scholar 

  • Pinto CB, Hall BK (1991) Toward an understanding of the epithelial requirement for osteogenesis in scleral mesenchyme of the embryonic chick. J Exp Zool 259:92–108

    Google Scholar 

  • Prieto AL, Jones FS, Cunningham BA, Crossin KL, Edelman GM (1990) Localization during development of alternatively spliced forms of cytotactin mRNA by in situ hybridization. J Cell Biol 111:685–698

    Google Scholar 

  • Pritchard JJ (1972) The osteoblast. In: Bourne GH (ed) The biochemistry and physiology of bone, vol 1. Academic Press, New York, pp 21–43

    Google Scholar 

  • Rhodes RK, Elmer WA (1975) Aberrant metabolism of matrix components in neonatal fibular cartilage of brachypod (bpH) mice. Dev Biol 46:14–27

    Google Scholar 

  • Richardson GP, Cossin KL, Chuong C-M, Edelman GM (1987) Expression of cell adhesion molecules during embryonic induction. II. Development of the otic placode. Dev Biol 119:217–230

    Google Scholar 

  • Riou JF, Shi D-L, Chiquet M, Bouchaut J-C (1988) Expression of tenascin in response to neural induction in amphibian embryos. Development 104:511–524

    Google Scholar 

  • Rodgers BJ, Kulyk WM, Kosher RA (1989) Stimulation of limb cartilage differentiation by cyclic AMP is dependent on cell density. Cell Differ Dev 28:179–188

    Google Scholar 

  • Ruberte E, Dolle P, Krust A, Zelent A, Morriss-Kay G, Chambon P (1990) Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development 108:213–222

    Google Scholar 

  • Sakakura T (1991) New aspects of stroma-parenchyma relations in mammary gland differentiation. Int Rev Cytol 125:165–202

    Google Scholar 

  • Salmivirta M, Elemius K, Vainio S, Hofer U, Chiquet-Ehrismann R, Thesleff I, Jalkanen M (1991) Syndecan from embryonic tooth mesenchyme binds tenascin. J Biol Chem 266:7733–7739

    Google Scholar 

  • Saunders JW, Jr (1948) The proximo-distal sequence of origin of the parts of the chick wing and the role of the ectoderm. J Exp Zool 108:363–404

    Google Scholar 

  • Sawyer RH, Fallon JF (1983) Epithelial-mesenchymal interactions in development. Praeger, New York

    Google Scholar 

  • Scott-Savage P, Hall BK (1979) The timing of the onset of osteogenesis in the tibia of the embryonic chick. J Morphol 162:454–464

    Google Scholar 

  • Scott-Savage P, Hall BK (1980) Differentiative ability of the tibial periosteum from the embryonic chick. Acta Anat 106:129–140

    Google Scholar 

  • Searls RL (1967) The role of cell migration in the development of the embryonic chick limb bud. J Exp Zool 166:39–50

    Google Scholar 

  • Searls RL (1973a) Chondrogenesis. In: Coward SJ (ed) Developmental regulation. Aspects of cell differentiation. Academic Press, New York, pp 219–251

    Google Scholar 

  • Searls RL (1973b) Newer knowledge of chondrogenesis. Clin Orthop 96:327–344

    Google Scholar 

  • Searls RL, Janners MY (1971) The initiation of limb bud outgrowth in the embryonic chick. Dev Biol 24:198–213

    Google Scholar 

  • Searls RL, Hilfer SR, Mirow SM (1972) An untrastructural study of early chondrogenesis in the chick wing bud. Dev Biol 28:123–137

    Google Scholar 

  • Shames RB, Jennings AG, Sawyer RH (1991) The initial expression and patterned appearance of tenascin in scutate scales is absent from the dermis of the scaleless (sc/sc) chicken. Dev Biol 147:174–186

    Google Scholar 

  • Shubin N, Alberch P (1986) A morphogenetic approach to the origin and basic organization of the tetrapod limb. Evol Biol 20:319–388

    Google Scholar 

  • Smith MM, Hall BK (1990) Evolutionary and developmental origins of vertebrate skeletogenic and odontogenic tissues. Biol Rev 65:277–374

    Google Scholar 

  • Solursh M (1983) Cell-cell interactions and chondrogenesis. In: Hall BK (ed) Cartilage, vol 2. Development, differentiation and growth. Academic Press, New York, pp 121–141

    Google Scholar 

  • Solursh M (1990) The role of extracellular matrix molecules in early limb development. Semin Dev Biol 1:45–53

    Google Scholar 

  • Solursh M, Ahrens PB, Reiter RS (1978) A tissue culture analysis of the steps in limb chondrogenesis. In vitro 14:51–61

    Google Scholar 

  • Steinberg MS (1963) Reconstruction of tissues by dissociated cells. Science 141:401–408

    Google Scholar 

  • Stern C, Sisodiya S, Keynes R (1986) Interactions between neurites and somite cells: inhibition and stimulation of nerve growth in the chick embryo. J Embryol Exp Morphol 91:209–226

    Google Scholar 

  • Stopak D, Harris AK (1982) Connective tissue morphogenesis by fibroblast traction. 1. Tissue culture observations. Dev Biol 90:383–398

    Google Scholar 

  • Stuart ES, Garber B, Moscona AA (1972) An analysis of feather germ formation in the embryo and in vitro, in normal development and in skin treated with hydrocortisone. J Exp Zool 179:97–118

    Google Scholar 

  • Summerbell D (1981) Evidence for regulation of growth, size and pattern in the developing chick limb bud. J Embryol Exp Morphol 65 [Suppl] 129–150

    Google Scholar 

  • Summerbell D, Wolpert L (1972) Cell density and cell division in the early morphogenesis of the chick wing. Nature New Biol 239:24–26

    Google Scholar 

  • Summerbell D, Wolpert L (1973) Precision of development in chick limb morphogenesis. Nature 244:228–230

    Google Scholar 

  • Thesleff I, Mackie E, Vainio S, Chiquet-Ehrismann R (1987) Changes in the distribution of tenascin during tooth development. Development 101:289–296

    Google Scholar 

  • Thesleff I, Kantomaa T, Mackie E, Chiquet-Ehrismann R (1988) Immunohistochemical localization of the matrix glycoprotein tenascin in the skull of the growing rat. Arch Oral Biol 33:383–390

    Google Scholar 

  • Thesleff I, Vaahtokari A, Vainio S (1990a) Molecular changes during determination and differentiation of the dental mesenchymal cell lineage. J Biol Buccale 18:179–188

    Google Scholar 

  • Thesleff I, Vainio S, Salmivirta M, Jalkanen M (1990b) Syndecan and tenascin: induction during early tooth morphogenesis and possible interactions. Cell Differ Dev 32:383–390

    Google Scholar 

  • Thompson TJ, Owens PDA, Wilson DJ (1989) Intramembranous osteogenesis and angiogenesis in the chick embryo. J Anat 166:55–65

    Google Scholar 

  • Thomson KS (1991) Parallelism and convergence in the horse limb: the internal-external dichotomy. In: Waren L, Kropowski H (eds) New perspectives on evolution. Wiley-Liss, New York, pp 101–122

    Google Scholar 

  • Thorogood PV (1983) Morphogenesis of cartilage. In: Hall BK (ed) Cartilage, vol 2. Development, differentiation and growth. Academic Press, New York, pp 223–254

    Google Scholar 

  • Thorogood PV, Hinchliffe JR (1975) An analysis of the condensation process during chondrogenesis in the embryonic chick hind limb. J Embryol Exp Morphol 33:581–606

    Google Scholar 

  • Toole BP, Trelstad RL (1971) Hyaluronate production and removal during corneal development in the chick. Dev Biol 26:28–35

    Google Scholar 

  • Toole BP, Jackson G, Gross J (1972) Hyaluronate in morphogenesis: inhibition of chondrogenesis in vitro. Proc Natl Acad Sci USA 69:1384–1386

    Google Scholar 

  • Tosney KW, Oakley RA (1990) The perinotochordal mesenchyme acts as a barrier to axon advance in the chick embryo: implications for a general mechanism of axonal guidance. Exp Neurol 109:75–89

    Google Scholar 

  • Trautman MS, Kimelman J, Bernfield M (1991) Developmental expression of syndecan, an integral membrane proteoglycan, correlates with cell differentiation. Development 111:213–220

    Google Scholar 

  • Tucker RP (1991) The sequential expression of tenascin mRNA in epithelium and mesenchyme during feather morphogenesis. W Roux's Arch Dev Biol 200:108–112

    Google Scholar 

  • Umansky R (1966) The effect of cell population density on the developmental state of reaggregated mouse limb mesenchyme. Dev Biol 13:31–56

    Google Scholar 

  • Upholt WB, Olsen BR (1991) The active genes of cartilage. In: Hall BK, Newman SA (eds) Cartilage: molecular aspects. CRC Press, Boca Raton, pp 1–57

    Google Scholar 

  • Wessells NK (1965) Morphology and proliferation during early feather development. Dev Biol 12:131–153

    Google Scholar 

  • Yokouchi Y, Sasaki H, Kuroiwa A (1991) Homeobox gene expression correlates with the bifurcation process of limb development. Nature 353:443–445

    Google Scholar 

  • Zernik J, Twarog K, Upholt WB (1990) Regulation of alkaline phosphatase and alpha 2 (I) procollagen synthesis during early intramembranous bone formation in the rat mandible. Differentiation 44:207–215

    Google Scholar 

  • Zimmermann B (1984) Assembly and disassembly of gap junctions during mesenchymal cell condensation and early chondrogenesis in limb buds of mouse embryos. J Anat 138:351–363

    Google Scholar 

  • Zimmermann B, Scharlach E, Kaatz R (1982) Cell contact and surface coat alterations of limb-bud mesenchymal cells during differentiation. J Embryol Exp Morphol 72:1–18

    Google Scholar 

  • Zimmermann B, Thies M (1984) Alterations of lectin binding during chondrogenesis of mouse limb buds. Histochemistry 81:353–362

    Google Scholar 

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  1. Department of Biology, Life Sciences Centre, Dalhousie University, B3H4J1, Nova Scotia, Halifax, Canada

    B. K. Hall & T. Miyake

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Hall, B.K., Miyake, T. The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anat Embryol 186, 107–124 (1992). https://doi.org/10.1007/BF00174948

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