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The developmental roles of the extracellular matrix: beyond structure to regulation

Abstract

Cells in multicellular organisms are surrounded by a complex three-dimensional macromolecular extracellular matrix (ECM). This matrix, traditionally thought to serve a structural function providing support and strength to cells within tissues, is increasingly being recognized as having pleiotropic effects in development and growth. Elucidation of the role that the ECM plays in developmental processes has been significantly advanced by studying the phenotypic and developmental consequences of specific genetic alterations of ECM components in the mouse. These studies have revealed the enormous contribution of the ECM to the regulation of key processes in morphogenesis and organogenesis, such as cell adhesion, proliferation, specification, migration, survival, and differentiation. The ECM interacts with signaling molecules and morphogens thereby modulating their activities. This review considers these advances in our understanding of the function of ECM proteins during development, extending beyond their structural capacity, to embrace their new roles in intercellula signaling.

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References

  • Abrass CK, Berfield AK, Ryan MC, Carter WG, Hansen KM (2006) Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene. Kidney Int 70:1062–1071

    CAS  PubMed  Article  Google Scholar 

  • Akimov SS, Belkin AM (2001) Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin: a role in TGFbeta-dependent matrix deposition. J Cell Sci 114:2989–3000

    CAS  PubMed  Google Scholar 

  • Akita K, Holst A von, Furukawa Y, Mikami T, Sugahara K, Faissner A (2008) Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic regions of the embryonic and adult central nervous system implies that complex chondroitin sulfates have a role in neural stem cell maintenance. Stem Cells 26:798–809

    CAS  PubMed  Article  Google Scholar 

  • Akiyama H, Chaboissier MC, Martin JF, Schedl A, Crombrugghe B de (2002) The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev 16:2813–2828

    CAS  PubMed  Article  Google Scholar 

  • Akiyama T, Kamimura K, Firkus C, Takeo S, Shimmi O, Nakato H (2008) Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surface. Dev Biol 313:408–419

    CAS  PubMed  Article  Google Scholar 

  • Ambrosio AL, Taelman VF, Lee HX, Metzinger CA, Coffinier C, De Robertis EM (2008) Crossveinless-2 is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning. Dev Cell 15:248–260

    CAS  PubMed  Article  Google Scholar 

  • Ameye L, Aria D, Jepsen K, Oldberg A, Xu T, Young MF (2002) Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16:673–680

    CAS  PubMed  Article  Google Scholar 

  • Andressen C, Arnhold S, Puschmann M, Bloch W, Hescheler J, Fassler R, Addicks K (1998) Beta1 integrin deficiency impairs migration and differentiation of mouse embryonic stem cell derived neurons. Neurosci Lett 251:165–168

    Article  Google Scholar 

  • Andrikopoulos K, Liu X, Keene DR, Jaenisch R, Ramirez F (1995) Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nat Genet 9:31–36

    CAS  PubMed  Article  Google Scholar 

  • Aouacheria A, Geourjon C, Aghajari N, Navratil V, Deleage G, Lethias C, Exposito JY (2006) Insights into early extracellular matrix evolution: spongin short chain collagen-related proteins are homologous to basement membrane type IV collagens and form a novel family widely distributed in invertebrates. Mol Biol Evol 23:2288–2302

    CAS  PubMed  Article  Google Scholar 

  • Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y (1999) Perlecan is essential for cartilage and cephalic development. Nat Genet 23:354–358

    CAS  PubMed  Article  Google Scholar 

  • Arteaga-Solis E, Gayraud B, Lee SY, Shum L, Sakai L, Ramirez F (2001) Regulation of limb patterning by extracellular microfibrils. J Cell Biol 154:275–281

    CAS  PubMed  Article  Google Scholar 

  • Aszodi A, Chan D, Hunziker E, Bateman JF, Fassler R (1998) Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol 143:1399–1412

    CAS  PubMed  Article  Google Scholar 

  • Aszodi A, Hunziker EB, Brakebusch C, Fassler R (2003) Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis. Genes Dev 17:2465–2479

    CAS  PubMed  Article  Google Scholar 

  • Aszodi A, Legate KR, Nakchbandi I, Fassler R (2006) What mouse mutants teach us about extracellular matrix function. Annu Rev Cell Dev Biol 22:591–621

    CAS  PubMed  Article  Google Scholar 

  • Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332

    CAS  PubMed  Article  Google Scholar 

  • Banos CC, Thomas AH, Kuo CK (2008) Collagen fibrillogenesis in tendon development: current models and regulation of fibril assembly. Birth Defects Res C Embryo Today 84:228–244

    CAS  PubMed  Article  Google Scholar 

  • Barrionuevo F, Taketo MM, Scherer G, Kispert A (2006) Sox9 is required for notochord maintenance in mice. Dev Biol 295:128–140

    CAS  PubMed  Article  Google Scholar 

  • Bell DM, Leung KK, Wheatley SC, Ng LJ, Zhou S, Ling KW, Sham MH, Koopman P, Tam PP, Cheah KS (1997) SOX9 directly regulates the type-II collagen gene. Nat Genet 16:174–178

    CAS  PubMed  Article  Google Scholar 

  • Bi W, Deng JM, Zhang Z, Behringer RR, Crombrugghe B de (1999) Sox9 is required for cartilage formation. Nat Genet 22:85–89

    CAS  PubMed  Article  Google Scholar 

  • Bi Y, Stuelten CH, Kilts T, Wadhwa S, Iozzo RV, Robey PG, Chen XD, Young MF (2005) Extracellular matrix proteoglycans control the fate of bone marrow stromal cells. J Biol Chem 280:30481–30489

    CAS  PubMed  Article  Google Scholar 

  • Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227

    CAS  PubMed  Article  Google Scholar 

  • Bier E (2008) Intriguing extracellular regulation of BMP signaling. Dev Cell 15:176–177

    CAS  PubMed  Article  Google Scholar 

  • Bridgewater LC, Walker MD, Miller GC, Ellison TA, Holsinger LD, Potter JL, Jackson TL, Chen RK, Winkel VL, Zhang Z, McKinney S, Crombrugghe B de (2003) Adjacent DNA sequences modulate Sox9 transcriptional activation at paired Sox sites in three chondrocyte-specific enhancer elements. Nucleic Acids Res 31:1541–1553

    CAS  PubMed  Article  Google Scholar 

  • Bronner-Fraser M (1988) Distribution and function of tenascin during cranial neural crest development in the chick. J Neurosci Res 21:135–147

    Article  Google Scholar 

  • Bulow HE, Hobert O (2006) The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22:375–407

    CAS  PubMed  Article  Google Scholar 

  • Cardoso WV, Lu J (2006) Regulation of early lung morphogenesis: questions, facts and controversies. Development 133:1611–1624

    CAS  PubMed  Article  Google Scholar 

  • Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H (1998) Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 141:1277–1286

    CAS  PubMed  Article  Google Scholar 

  • Chakravarti S, Zhang G, Chervoneva I, Roberts L, Birk DE (2006) Collagen fibril assembly during postnatal development and dysfunctional regulation in the lumican-deficient murine cornea. Dev Dyn 235:2493–2506

    CAS  PubMed  Article  Google Scholar 

  • Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT, Wei K, Helms JA, Kuo CJ, Kraft DL, Weissman IL (2009) Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature 457:490–494

    CAS  PubMed  Article  Google Scholar 

  • Chang W, Lin Z, Kulessa H, Hebert J, Hogan BL, Wu DK (2008) Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet 4:e1000050

    PubMed  Article  CAS  Google Scholar 

  • Cheah KSE, Wong SYY, Zhang JCL, Leung AWL, Chan D, Tam PPL (2005) Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels. Mech Dev 122 (Supp 1):S25

    Google Scholar 

  • Chen ZL, Strickland S (2003) Laminin gamma1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve. J Cell Biol 163:889–899

    CAS  PubMed  Article  Google Scholar 

  • Coles EG, Gammill LS, Miner JH, Bronner-Fraser M (2006) Abnormalities in neural crest cell migration in laminin alpha5 mutant mice. Dev Biol 289:218–228

    CAS  PubMed  Article  Google Scholar 

  • Cortes M, Baria AT, Schwartz NB (2009) Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate. Development 136:1697–1706

    CAS  PubMed  Article  Google Scholar 

  • Costa-Silva B, Costa MC da, Melo FR, Neves CM, Alvarez-Silva M, Calloni GW, Trentin AG (2009) Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential. Exp Cell Res 315:955–967

    CAS  PubMed  Article  Google Scholar 

  • Costantini F, Shakya R (2006) GDNF/Ret signaling and the development of the kidney. Bioessays 28:117–127

    CAS  PubMed  Article  Google Scholar 

  • Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R (1999) Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147:1109–1122

    CAS  PubMed  Article  Google Scholar 

  • Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136:729–743

    CAS  PubMed  Article  Google Scholar 

  • De Moerlooze L, Spencer-Dene B, Revest JM, Hajihosseini M, Rosewell I, Dickson C (2000) An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development 127:483–492

    PubMed  Google Scholar 

  • Delannet M, Martin F, Bossy B, Cheresh DA, Reichardt LF, Duband JL (1994) Specific roles of the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins in avian neural crest cell adhesion and migration on vitronectin. Development 120:2687–2702

    CAS  PubMed  Google Scholar 

  • Drago J, Nurcombe V, Bartlett PF (1991) Laminin through its long arm E8 fragment promotes the proliferation and differentiation of murine neuroepithelial cells in vitro. Exp Cell Res 192:256–265

    CAS  PubMed  Article  Google Scholar 

  • Duband JL, Thiery JP (1987) Distribution of laminin and collagens during avian neural crest development. Development 101:461–478

    CAS  PubMed  Google Scholar 

  • Duband JL, Rocher S, Yamada KM, Thiery JP (1986) Interactions of migrating neural crest cells with fibronectin. Prog Clin Biol Res 226:127–139

    CAS  PubMed  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689

    CAS  PubMed  Article  Google Scholar 

  • Engler AJ, Carag-Krieger C, Johnson CP, Raab M, Tang HY, Speicher DW, Sanger JW, Sanger JM, Discher DE (2008) Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating. J Cell Sci 121:3794–3802

    CAS  PubMed  Article  Google Scholar 

  • Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, Hayashi Y, Ohuchi H, Falahat B, Bolstad AI, Jonsson R, Wahren-Herlenius M, Dahl N (2005) Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands. Nat Genet 37:125–127

    CAS  PubMed  Article  Google Scholar 

  • Esko JD, Selleck SB (2002) Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem 71:435–471

    CAS  PubMed  Article  Google Scholar 

  • Flanagan LA, Rebaza LM, Derzic S, Schwartz PH, Monuki ES (2006) Regulation of human neural precursor cells by laminin and integrins. J Neurosci Res 83:845–856

    CAS  Google Scholar 

  • Fontana L, Chen Y, Prijatelj P, Sakai T, Fassler R, Sakai LY, Rifkin DB (2005) Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J 19:1798–1808

    CAS  PubMed  Article  Google Scholar 

  • Fox MA, Sanes JR, Borza DB, Eswarakumar VP, Fassler R, Hudson BG, John SW, Ninomiya Y, Pedchenko V, Pfaff SL, Rheault MN, Sado Y, Segal Y, Werle MJ, Umemori H (2007) Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals. Cell 129:179–193

    CAS  PubMed  Article  Google Scholar 

  • Fujiwara H, Hayashi Y, Sanzen N, Kobayashi R, Weber CN, Emoto T, Futaki S, Niwa H, Murray P, Edgar D, Sekiguchi K (2007) Regulation of mesodermal differentiation of mouse embryonic stem cells by basement membranes. J Biol Chem 282:29701–29711

    CAS  PubMed  Article  Google Scholar 

  • Gao J, DeRouen MC, Chen CH, Nguyen M, Nguyen NT, Ido H, Harada K, Sekiguchi K, Morgan BA, Miner JH, Oro AE, Marinkovich MP (2008) Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. Genes Dev 22:2111–2124

    CAS  PubMed  Article  Google Scholar 

  • Gautam M, Noakes PG, Moscoso L, Rupp F, Scheller RH, Merlie JP, Sanes JR (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85:525–535

    CAS  PubMed  Article  Google Scholar 

  • George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes RO (1993) Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119:1079–1091

    CAS  PubMed  Google Scholar 

  • Goh KL, Yang JT, Hynes RO (1997) Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos. Development 124:4309–4319

    CAS  PubMed  Google Scholar 

  • Gondo Y (2008) Trends in large-scale mouse mutagenesis: from genetics to functional genomics. Nat Rev Genet 9:803–810

    CAS  PubMed  Article  Google Scholar 

  • Gordon MK, Hahn RA (2009) Collagens. Cell Tissue Res (this issue)

  • Gotz W, Osmers R, Herken R (1995) Localisation of extracellular matrix components in the embryonic human notochord and axial mesenchyme. J Anat 186:111–121

    PubMed  Google Scholar 

  • Han Y, Lefebvre V (2008) L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer. Mol Cell Biol 28:4999–5013

    CAS  PubMed  Article  Google Scholar 

  • Harada M, Murakami H, Okawa A, Okimoto N, Hiraoka S, Nakahara T, Akasaka R, Shiraishi Y, Futatsugi N, Mizutani-Koseki Y, Kuroiwa A, Shirouzu M, Yokoyama S, Taiji M, Iseki S, Ornitz DM, Koseki H (2009) FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion. Nat Genet 41:289–298

    CAS  PubMed  Article  Google Scholar 

  • Hashizume A, Hieda Y (2006) Hedgehog peptide promotes cell polarization and lumen formation in developing mouse submandibular gland. Biochem Biophys Res Commun 339:996–1000

    CAS  PubMed  Article  Google Scholar 

  • Hayes AJ, Benjamin M, Ralphs JR (2001) Extracellular matrix in development of the intervertebral disc. Matrix Biol 20:107–121

    CAS  PubMed  Article  Google Scholar 

  • Heino J (2007) The collagen family members as cell adhesion proteins. Bioessays 29:1001–1010

    CAS  PubMed  Article  Google Scholar 

  • Henriquez JP, Webb A, Bence M, Bildsoe H, Sahores M, Hughes SM, Salinas PC (2008) Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin. Proc Natl Acad Sci USA 105:18812–18817

    CAS  PubMed  Article  Google Scholar 

  • 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

    CAS  PubMed  Article  Google Scholar 

  • Holster T, Pakkanen O, Soininen R, Sormunen R, Nokelainen M, Kivirikko KI, Myllyharju J (2007) Loss of assembly of the main basement membrane collagen, type IV, but not fibril-forming collagens and embryonic death in collagen prolyl 4-hydroxylase I null mice. J Biol Chem 282:2512–2519

    CAS  PubMed  Article  Google Scholar 

  • Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60

    CAS  PubMed  Article  Google Scholar 

  • Ikeya M, Nosaka T, Fukushima K, Kawada M, Furuta Y, Kitamura T, Sasai Y (2008) Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice. Mech Dev 125:832–842

    CAS  PubMed  Article  Google Scholar 

  • Jaskoll T, Melnick M (1999) Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations. Anat Rec 256:252–268

    CAS  PubMed  Article  Google Scholar 

  • Jaskoll T, Zhou YM, Chai Y, Makarenkova HP, Collinson JM, West JD, Hajihosseini MK, Lee J, Melnick M (2002) Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+/Delta), BMP7(-/-) and Pax6(-/-) mice. Cells Tissues Organs 170:83–98

    CAS  PubMed  Article  Google Scholar 

  • Jaskoll T, Leo T, Witcher D, Ormestad M, Astorga J, Bringas P Jr, Carlsson P, Melnick M (2004a) Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis. Dev Dyn 229:722–732

    CAS  PubMed  Article  Google Scholar 

  • Jaskoll T, Witcher D, Toreno L, Bringas P, Moon AM, Melnick M (2004b) FGF8 dose-dependent regulation of embryonic submandibular salivary gland morphogenesis. Dev Biol 268:457–469

    CAS  PubMed  Article  Google Scholar 

  • Jaskoll T, Abichaker G, Witcher D, Sala FG, Bellusci S, Hajihosseini MK, Melnick M (2005) FGF10/FGFR2b signaling plays essential roles during in vivo embryonic submandibular salivary gland morphogenesis. BMC Dev Biol 5:11

    PubMed  Article  CAS  Google Scholar 

  • Jia J, Maccarana M, Zhang X, Bespalov M, Lindahl U, Li JP (2009) Lack of L-iduronic acid in heparan sulfate affects interaction with growth factors and cell signaling. J Biol Chem 284:15942–15950

    CAS  PubMed  Article  Google Scholar 

  • Kadler KE, Hill A, Canty-Laird EG (2008) Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Curr Opin Cell Biol 20:495–501

    CAS  PubMed  Article  Google Scholar 

  • Kalyani A, Hobson K, Rao MS (1997) Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis. Dev Biol 186:202–223

    CAS  PubMed  Article  Google Scholar 

  • Kearns SM, Laywell ED, Kukekov VK, Steindler DA (2003) Extracellular matrix effects on neurosphere cell motility. Exp Neurol 182:240–244

    CAS  PubMed  Article  Google Scholar 

  • Khetarpal U, Robertson NG, Yoo TJ, Morton CC (1994) Expression and localization of COL2A1 mRNA and type II collagen in human fetal cochlea. Hear Res 79:59–73

    CAS  PubMed  Article  Google Scholar 

  • Khoshnoodi J, Pedchenko V, Hudson BG (2008) Mammalian collagen IV. Microsc Res Tech 71:357–370

    CAS  PubMed  Article  Google Scholar 

  • Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423:332–336

    CAS  PubMed  Article  Google Scholar 

  • Krotoski DM, Bronner-Fraser M (1986) Mapping of neural crest pathways in Xenopus laevis. Prog Clin Biol Res 217B:229–233

    CAS  PubMed  Google Scholar 

  • Ksiazek I, Burkhardt C, Lin S, Seddik R, Maj M, Bezakova G, Jucker M, Arber S, Caroni P, Sanes JR, Bettler B, Ruegg MA (2007) Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death. J Neurosci 27:7183–7195

    CAS  PubMed  Article  Google Scholar 

  • Kukekov VG, Laywell ED, Suslov O, Davies K, Scheffler B, Thomas LB, O’Brien TF, Kusakabe M, Steindler DA (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain. Exp Neurol 156:333–344

    CAS  PubMed  Article  Google Scholar 

  • Lallier T, Leblanc G, Artinger KB, Bronner-Fraser M (1992) Cranial and trunk neural crest cells use different mechanisms for attachment to extracellular matrices. Development 116:531–541

    CAS  PubMed  Google Scholar 

  • Landolt RM, Vaughan L, Winterhalter KH, Zimmermann DR (1995) Versican is selectively expressed in embryonic tissues that act as barriers to neural crest cell migration and axon outgrowth. Development 121:2303–2312

    CAS  PubMed  Google Scholar 

  • Larrain J, Bachiller D, Lu B, Agius E, Piccolo S, De Robertis EM (2000) BMP-binding modules in chordin: a model for signalling regulation in the extracellular space. Development 127:821–830

    CAS  PubMed  Google Scholar 

  • Laywell ED, Kukekov VG, Steindler DA (1999) Multipotent neurospheres can be derived from forebrain subependymal zone and spinal cord of adult mice after protracted postmortem intervals. Exp Neurol 156:430–433

    CAS  PubMed  Article  Google Scholar 

  • Laywell ED, Rakic P, Kukekov VG, Holland EC, Steindler DA (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA 97:13883-13888

    CAS  PubMed  Article  Google Scholar 

  • Le Douarin N (2001) The neural crest and evolution of vertebrates (in French). Bull Mem Acad R Med Belg 156:521–531

    PubMed  Google Scholar 

  • Lefebvre V, Huang W, Harley VR, Goodfellow PN, Crombrugghe B de (1997) SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene. Mol Cell Biol 17:2336–2346

    CAS  PubMed  Google Scholar 

  • Leone DP, Relvas JB, Campos LS, Hemmi S, Brakebusch C, Fassler R, Ffrench-Constant C, Suter U (2005) Regulation of neural progenitor proliferation and survival by beta1 integrins. J Cell Sci 118:2589-2599

    CAS  PubMed  Article  Google Scholar 

  • Li H, Corrales CE, Wang Z, Zhao Y, Wang Y, Liu H, Heller S (2005) BMP4 signaling is involved in the generation of inner ear sensory epithelia. BMC Dev Biol 5:16

    CAS  PubMed  Article  Google Scholar 

  • Li J, Tzu J, Chen Y, Zhang YP, Nguyen NT, Gao J, Bradley M, Keene DR, Oro AE, Miner JH, Marinkovich MP (2003) Laminin-10 is crucial for hair morphogenesis. EMBO J 22:2400–2410

    CAS  PubMed  Article  Google Scholar 

  • Li SW, Prockop DJ, Helminen H, Fassler R, Lapvetelainen T, Kiraly K, Peltarri A, Arokoski J, Lui H, Arita M (1995) Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone. Genes Dev 9:2821–2830

    CAS  PubMed  Article  Google Scholar 

  • Li SW, Takanosu M, Arita M, Bao Y, Ren ZX, Maier A, Prockop DJ, Mayne R (2001) Targeted disruption of Col11a2 produces a mild cartilage phenotype in transgenic mice: comparison with the human disorder otospondylomegaepiphyseal dysplasia (OSMED). Dev Dyn 222:141–152

    CAS  PubMed  Article  Google Scholar 

  • Li Y, Lacerda DA, Warman ML, Beier DR, Yoshioka H, Ninomiya Y, Oxford JT, Morris NP, Andrikopoulos K, Ramirez F (1995) A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis. Cell 80:423–430

    CAS  PubMed  Article  Google Scholar 

  • Libby RT, Lavallee CR, Balkema GW, Brunken WJ, Hunter DD (1999) Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS. J Neurosci 19:9399–9411

    CAS  PubMed  Google Scholar 

  • Lincoln J, Florer JB, Deutsch GH, Wenstrup RJ, Yutzey KE (2006) ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development. Dev Dyn 235:3295–3305

    CAS  PubMed  Article  Google Scholar 

  • Linton JM, Martin GR, Reichardt LF (2007) The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Development 134:2501–2509

    CAS  PubMed  Article  Google Scholar 

  • Liu X, Wu H, Byrne M, Krane S, Jaenisch R (1997) Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Natl Acad Sci USA 94:1852–1856

    CAS  PubMed  Article  Google Scholar 

  • Lui VC, Ng LJ, Nicholls J, Tam PP, Cheah KS (1995) Tissue-specific and differential expression of alternatively spliced alpha 1(II) collagen mRNAs in early human embryos. Dev Dyn 203:198–211

    CAS  PubMed  Google Scholar 

  • Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81

    CAS  PubMed  Article  Google Scholar 

  • Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP (2003) Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130:3175–3185

    CAS  PubMed  Article  Google Scholar 

  • Mak AC, Szeto IY, Fritzsch B, Cheah KS (2009) Differential and overlapping expression pattern of SOX2 and SOX9 in inner ear development. Gene Expr Patterns 9:444–453

    CAS  PubMed  Article  Google Scholar 

  • Matthews HK, Marchant L, Carmona-Fontaine C, Kuriyama S, Larrain J, Holt MR, Parsons M, Mayor R (2008) Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA. Development 135:1771–1780

    CAS  PubMed  Article  Google Scholar 

  • Melrose J, Roughley P, Knox S, Smith S, Lord M, Whitelock J (2006) The structure, location, and function of perlecan, a prominent pericellular proteoglycan of fetal, postnatal, and mature hyaline cartilages. J Biol Chem 281:36905–36914

    CAS  PubMed  Article  Google Scholar 

  • Metzger RJ, Klein OD, Martin GR, Krasnow MA (2008) The branching programme of mouse lung development. Nature 453:745–750

    CAS  PubMed  Article  Google Scholar 

  • Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A (2004) Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development 131:3401–3410

    CAS  PubMed  Article  Google Scholar 

  • Michos O, Goncalves A, Lopez-Rios J, Tiecke E, Naillat F, Beier K, Galli A, Vainio S, Zeller R (2007) Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development 134:2397–2405

    CAS  PubMed  Article  Google Scholar 

  • Min H, Danilenko DM, Scully SA, Bolon B, Ring BD, Tarpley JE, DeRose M, Simonet WS (1998) Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev 12:3156–3161

    CAS  PubMed  Article  Google Scholar 

  • Miner JH, Li C (2000) Defective glomerulogenesis in the absence of laminin alpha5 demonstrates a developmental role for the kidney glomerular basement membrane. Dev Biol 217:278–289

    CAS  PubMed  Article  Google Scholar 

  • Miner JH, Cunningham J, Sanes JR (1998) Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 143:1713–1723

    CAS  PubMed  Article  Google Scholar 

  • Miner JH, Li C, Mudd JL, Go G, Sutherland AE (2004) Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development 131:2247–2256

    CAS  PubMed  Article  Google Scholar 

  • Monne M, Han L, Schwend T, Burendahl S, Jovine L (2008) Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats. Nature 456:653–657

    CAS  PubMed  Article  Google Scholar 

  • Murakami H, Okawa A, Yoshida H, Nishikawa S, Moriya H, Koseki H (2002) Elbow knee synostosis (Eks): a new mutation on mouse chromosome 14. Mamm Genome 13:341–344

    PubMed  Article  Google Scholar 

  • Murase S, Horwitz AF (2002) Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream. J Neurosci 22:3568–3579

    CAS  PubMed  Google Scholar 

  • Myllyharju J, Kivirikko KI (2004) Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet 20:33–43

    CAS  PubMed  Article  Google Scholar 

  • Nagai N, Hosokawa M, Itohara S, Adachi E, Matsushita T, Hosokawa N, Nagata K (2000) Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis. J Cell Biol 150:1499–1506

    CAS  PubMed  Article  Google Scholar 

  • Nakrieko KA, Welch I, Dupuis H, Bryce D, Pajak A, St AR, Dedhar S, D’Souza SJ, Dagnino L (2008) Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis. Mol Biol Cell 19:1462–1473

    CAS  PubMed  Article  Google Scholar 

  • Newgreen DF (1989) Physical influences on neural crest cell migration in avian embryos: contact guidance and spatial restriction. Dev Biol 131:136–148

    CAS  PubMed  Article  Google Scholar 

  • Newgreen D, Thiery JP (1980) Fibronectin in early avian embryos: synthesis and distribution along the migration pathways of neural crest cells. Cell Tissue Res 211:269–291

    CAS  PubMed  Article  Google Scholar 

  • Nguyen NM, Senior RM (2006) Laminin isoforms and lung development: all isoforms are not equal. Dev Biol 294:271–279

    CAS  PubMed  Article  Google Scholar 

  • Nguyen NM, Miner JH, Pierce RA, Senior RM (2002) Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung. Dev Biol 246:231–244

    CAS  PubMed  Article  Google Scholar 

  • Nguyen NM, Kelley DG, Schlueter JA, Meyer MJ, Senior RM, Miner JH (2005) Epithelial laminin alpha5 is necessary for distal epithelial cell maturation, VEGF production, and alveolization in the developing murine lung. Dev Biol 282:111–125

    CAS  PubMed  Article  Google Scholar 

  • Nishimune H, Valdez G, Jarad G, Moulson CL, Muller U, Miner JH, Sanes JR (2008) Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. J Cell Biol 182:1201–1215

    CAS  PubMed  Article  Google Scholar 

  • Noakes PG, Gautam M, Mudd J, Sanes JR, Merlie JP (1995a) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2. Nature 374:258–262

    CAS  PubMed  Article  Google Scholar 

  • Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP (1995b) The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet 10:400–406

    CAS  PubMed  Article  Google Scholar 

  • Novak U, Kaye AH (2000) Extracellular matrix and the brain: components and function. J Clin Neurosci 7:280–290

    CAS  PubMed  Article  Google Scholar 

  • Ornitz DM (2000) FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays 22:108–112

    CAS  PubMed  Article  Google Scholar 

  • Patel VN, Knox SM, Likar KM, Lathrop CA, Hossain R, Eftekhari S, Whitelock JM, Elkin M, Vlodavsky I, Hoffman MP (2007) Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis. Development 134:4177–4186

    CAS  PubMed  Article  Google Scholar 

  • Peacock JD, Lu Y, Koch M, Kadler KE, Lincoln J (2008) Temporal and spatial expression of collagens during murine atrioventricular heart valve development and maintenance. Dev Dyn 237:3051–3058

    PubMed  Article  Google Scholar 

  • Perris R, Krotoski D, Bronner-Fraser M (1991) Collagens in avian neural crest development: distribution in vivo and migration-promoting ability in vitro. Development 113:969–984

    CAS  Google Scholar 

  • Perris R, Kuo HJ, Glanville RW, Leibold S, Bronner-Fraser M (1993a) Neural crest cell interaction with type VI collagen is mediated by multiple cooperative binding sites within triple-helix and globular domains. Exp Cell Res 209:103–117

    CAS  PubMed  Article  Google Scholar 

  • Perris R, Syfrig J, Paulsson M, Bronner-Fraser M (1993b) Molecular mechanisms of neural crest cell attachment and migration on types I and IV collagen. J Cell Sci 106:1357–1368

    CAS  PubMed  Google Scholar 

  • Perris R, Perissinotto D, Pettway Z, Bronner-Fraser M, Morgelin M, Kimata K (1996) Inhibitory effects of PG-H/aggrecan and PG-M/versican on avian neural crest cell migration. FASEB J 10:293–301

    CAS  PubMed  Google Scholar 

  • Poschl E, Schlotzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U (2004) Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 131:1619–1628

    PubMed  Article  CAS  Google Scholar 

  • Pujades C, Kamaid A, Alsina B, Giraldez F (2006) BMP-signaling regulates the generation of hair-cells. Dev Biol 292:55–67

    CAS  PubMed  Article  Google Scholar 

  • Ramirez F, Sakai LY (2009) Biogenesis and function of fibrillin assemblies. Cell Tissue Res (this issue)

  • Rautavuoma K, Takaluoma K, Sormunen R, Myllyharju J, Kivirikko KI, Soininen R (2004) Premature aggregation of type IV collagen and early lethality in lysyl hydroxylase 3 null mice. Proc Natl Acad Sci USA 101:14120–14125

    CAS  PubMed  Article  Google Scholar 

  • Rebustini IT, Patel VN, Stewart JS, Layvey A, Georges-Labouesse E, Miner JH, Hoffman MP (2007) Laminin alpha5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through beta1 integrin signaling. Dev Biol 308:15–29

    CAS  PubMed  Article  Google Scholar 

  • Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.Science 255:1707-1710

    CAS  PubMed  Article  Google Scholar 

  • Ring C, Hassell J, Halfter W (1996) Expression pattern of collagen IX and potential role in the segmentation of the peripheral nervous system. Dev Biol 180:41–53

    CAS  PubMed  Article  Google Scholar 

  • Rodda SJ, McMahon AP (2006) Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133:3231–3244

    CAS  PubMed  Article  Google Scholar 

  • Rodgers KD, San Antonio JD, Jacenko O (2008) Heparan sulfate proteoglycans: a GAGgle of skeletal-hematopoietic regulators. Dev Dyn 237:2622–2642

    CAS  PubMed  Article  Google Scholar 

  • Rossi M, Morita H, Sormunen R, Airenne S, Kreivi M, Wang L, Fukai N, Olsen BR, Tryggvason K, Soininen R (2003) Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J 22:236–245

    CAS  PubMed  Article  Google Scholar 

  • Ruotsalainen H, Sipila L, Vapola M, Sormunen R, Salo AM, Uitto L, Mercer DK, Robins SP, Risteli M, Aszodi A, Fassler R, Myllyla R (2006) Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes. J Cell Sci 119:625–635

    CAS  PubMed  Article  Google Scholar 

  • Sakai T, Larsen M, Yamada KM (2003) Fibronectin requirement in branching morphogenesis. Nature 423:876–881

    CAS  PubMed  Article  Google Scholar 

  • Schuger L, O’Shea KS, Nelson BB, Varani J (1990a) Organotypic arrangement of mouse embryonic lung cells on a basement membrane extract: involvement of laminin. Development 110:1091–1099

    CAS  PubMed  Google Scholar 

  • Schuger L, O’Shea S, Rheinheimer J, Varani J (1990b) Laminin in lung development: effects of anti-laminin antibody in murine lung morphogenesis. Dev Biol 137:26–32

    CAS  PubMed  Article  Google Scholar 

  • Schuger L, Skubitz AP, O’Shea KS, Chang JF, Varani J (1991) Identification of laminin domains involved in branching morphogenesis: effects of anti-laminin monoclonal antibodies on mouse embryonic lung development. Dev Biol 146:531–541

    CAS  PubMed  Article  Google Scholar 

  • Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S (1999) Fgf10 is essential for limb and lung formation. Nat Genet 21:138–141

    CAS  PubMed  Article  Google Scholar 

  • Sengle G, Charbonneau NL, Ono RN, Sasaki T, Alvarez J, Keene DR, Bachinger HP, Sakai LY (2008) Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J Biol Chem 283:13874–13888

    CAS  PubMed  Article  Google Scholar 

  • Sirko S, Holst A von, Wizenmann A, Gotz M, Faissner A (2007) Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134:2727–2738

    CAS  PubMed  Article  Google Scholar 

  • Smirnov SP, Barzaghi P, McKee KK, Ruegg MA, Yurchenco PD (2005) Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering. J Biol Chem 280:41449–41457

    CAS  PubMed  Article  Google Scholar 

  • Smith SM, West LA, Govindraj P, Zhang X, Ornitz DM, Hassell JR (2007a) Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors. Matrix Biol 26:175–184

    CAS  PubMed  Article  Google Scholar 

  • Smith SM, West LA, Hassell JR (2007b) The core protein of growth plate perlecan binds FGF-18 and alters its mitogenic effect on chondrocytes. Arch Biochem Biophys 468:244–251

    CAS  PubMed  Article  Google Scholar 

  • Smits P, Lefebvre V (2003) Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs. Development 130:1135–1148

    CAS  PubMed  Article  Google Scholar 

  • Smits P, Li P, Mandel J, Zhang Z, Deng JM, Behringer RR, Crombrugghe B de, Lefebvre V (2001) The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell 1:277–290

    CAS  PubMed  Article  Google Scholar 

  • Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, Edgar D (1999) Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol 144:151–160

    CAS  PubMed  Article  Google Scholar 

  • So CL, Kaluarachchi K, Tam PP, Cheah KS (2001) Impact of mutations of cartilage matrix genes on matrix structure, gene activity and chondrogenesis. Osteoarthr Cartil 9 (Suppl A):S160–S173

    PubMed  Google Scholar 

  • Steinberg Z, Myers C, Heim VM, Lathrop CA, Rebustini IT, Stewart JS, Larsen M, Hoffman MP (2005) FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis. Development 132:1223–1234

    CAS  PubMed  Article  Google Scholar 

  • Stemple DL (2005) Structure and function of the notochord: an essential organ for chordate development. Development 132:2503–2512

    CAS  PubMed  Article  Google Scholar 

  • Strachan LR, Condic ML (2003) Neural crest motility and integrin regulation are distinct in cranial and trunk populations. Dev Biol 259:288-302

    CAS  PubMed  Article  Google Scholar 

  • Sugahara K, Mikami T (2007) Chondroitin/dermatan sulfate in the central nervous system. Curr Opin Struct Biol 17:

  • Sweeney E, Campbell M, Watkins K, Hunter CA, Jacenko O (2008) Altered endochondral ossification in collagen X mouse models leads to impaired immune responses. Dev Dyn 237:2693–2704

    CAS  PubMed  Article  Google Scholar 

  • Tan SS, Crossin KL, Hoffman S, Edelman GM (1987) Asymmetric expression in somites of cytotactin and its proteoglycan ligand is correlated with neural crest cell distribution. Proc Natl Acad Sci USA 84:7977–7981

    CAS  PubMed  Article  Google Scholar 

  • Testaz S, Duband JL (2001) Central role of the alpha4beta1 integrin in the coordination of avian truncal neural crest cell adhesion, migration, and survival. Dev Dyn 222:127–140

    CAS  PubMed  Article  Google Scholar 

  • Tholozan FM, Gribbon C, Li Z, Goldberg MW, Prescott AR, McKie N, Quinlan RA (2007) FGF-2 release from the lens capsule by MMP-2 maintains lens epithelial cell viability. Mol Biol Cell 18:4222–4231

    CAS  PubMed  Article  Google Scholar 

  • Tiainen P, Pasanen A, Sormunen R, Myllyharju J (2008) Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J Biol Chem 283:19432–19439

    CAS  PubMed  Article  Google Scholar 

  • Tucker RP, McKay SE (1991) The expression of tenascin by neural crest cells and glia. Development 112:1031–1039

    CAS  PubMed  Google Scholar 

  • Wagenseil JE, Mecham RP (2007) New insights into elastic fiber assembly. Birth Defects Res C Embryo Today 81:229–240

    CAS  PubMed  Article  Google Scholar 

  • Wai AW, Ng LJ, Watanabe H, Yamada Y, Tam PP, Cheah KS (1998) Disrupted expression of matrix genes in the growth plate of the mouse cartilage matrix deficiency (cmd) mutant. Dev Genet 22:349–358

    CAS  PubMed  Article  Google Scholar 

  • Wang J, Ruan NJ, Qian L, Lei WL, Chen F, Luo ZG (2008) Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction. J Biol Chem 283:21668–21675

    CAS  PubMed  Article  Google Scholar 

  • Wang X, Harris RE, Bayston LJ, Ashe HL (2008) Type IV collagens regulate BMP signalling in Drosophila. Nature 455:72–77

    CAS  PubMed  Article  Google Scholar 

  • Wassarman PM, Jovine L, Litscher ES (2004) Mouse zona pellucida genes and glycoproteins. Cytogenet Genome Res 105:228–234

    CAS  PubMed  Article  Google Scholar 

  • Watanabe H, Yamada Y (1999) Mice lacking link protein develop dwarfism and craniofacial abnormalities. Nat Genet 21:225–229

    CAS  PubMed  Article  Google Scholar 

  • Watanabe H, Kimata K, Line S, Strong D, Gao LY, Kozak CA, Yamada Y (1994) Mouse cartilage matrix deficiency (cmd) caused by a 7 bp deletion in the aggrecan gene. Nat Genet 7:154–157

    CAS  PubMed  Article  Google Scholar 

  • Wells RG, Discher DE (2008) Matrix elasticity, cytoskeletal tension, and TGF-beta: the insoluble and soluble meet. Sci Signal 1:e13

    Google Scholar 

  • Wenstrup RJ, Florer JB, Davidson JM, Phillips CL, Pfeiffer BJ, Menezes DW, Chervoneva I, Birk DE (2006) Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages. J Biol Chem 281:12888–12895

    CAS  PubMed  Article  Google Scholar 

  • Whitelock JM, Melrose J, Iozzo RV (2008) Diverse cell signaling events modulated by perlecan. Biochemistry 47:11174–11183

    CAS  PubMed  Article  Google Scholar 

  • Yamamoto S, Fukumoto E, Yoshizaki K, Iwamoto T, Yamada A, Tanaka K, Suzuki H, Aizawa S, Arakaki M, Yuasa K, Oka K, Chai Y, Nonaka K, Fukumoto S (2008) Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression. J Biol Chem 283:23139–23149

    CAS  PubMed  Article  Google Scholar 

  • Yao Y, Zebboudj AF, Shao E, Perez M, Bostrom K (2006) Regulation of bone morphogenetic protein-4 by matrix GLA protein in vascular endothelial cells involves activin-like kinase receptor 1. J Biol Chem 281:33921–33930

    CAS  PubMed  Article  Google Scholar 

  • Yao Y, Nowak S, Yochelis A, Garfinkel A, Bostrom KI (2007) Matrix GLA protein, an inhibitory morphogen in pulmonary vascular development. J Biol Chem 282:30131–30142

    CAS  PubMed  Article  Google Scholar 

  • Yao Y, Shahbazian A, Bostrom KI (2008) Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. Circ Res 102:1065–1074

    CAS  PubMed  Article  Google Scholar 

  • Yoon BS, Ovchinnikov DA, Yoshii I, Mishina Y, Behringer RR, Lyons KM (2005) Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci USA 102:5062–5067

    CAS  PubMed  Article  Google Scholar 

  • Yu J, McMahon AP, Valerius MT (2004) Recent genetic studies of mouse kidney development. Curr Opin Genet Dev 14:550–557

    CAS  PubMed  Article  Google Scholar 

  • Yu WM, Feltri ML, Wrabetz L, Strickland S, Chen ZL (2005) Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci 25:4463–4472

    CAS  PubMed  Article  Google Scholar 

  • Yurchenco PD, Amenta PS, Patton BL (2004) Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol 22:521–538

    CAS  PubMed  Article  Google Scholar 

  • Zakin L, Metzinger CA, Chang EY, Coffinier C, De Robertis EM (2008) Development of the vertebral morphogenetic field in the mouse: interactions between crossveinless-2 and twisted gastrulation. Dev Biol 323:6–18

    CAS  PubMed  Article  Google Scholar 

  • Zhu Y, Oganesian A, Keene DR, Sandell LJ (1999) Type IIA procollagen containing the cysteine-rich amino propeptide is deposited in the extracellular matrix of prechondrogenic tissue and binds to TGF-beta1 and BMP-2. J Cell Biol 144:1069–1080

    CAS  PubMed  Article  Google Scholar 

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Correspondence to Kathryn S. E. Cheah.

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The authors are supported by the University Grants Committee of Hong Kong Area of Excellence programme AoE/M-04/04.

Box 1: introduction to some basic ECM molecules and structures

Box 1: introduction to some basic ECM molecules and structures

Collagens

Collagens are triple helical proteins that confer compressive and tensile strength to animal tissues and serve as anchors for cell adhesion through surface receptors. To date, more than 40 mammalian genes encoding collagen α chains have been described, the products of which combine to form at least 28 distinct homo- and heterotrimeric molecules (Myllyharju and Kivirikko 2004; Heino 2007; Gordon and Hahn 2009). The collagen proteins differ considerably in size, structure, tissue distribution, and function, but all are characterized by the presence of either continuous or interrupted triple-helical domains made up of repeating Gly–X–Y motifs. Collagen subfamily members form different supramolecular structures such as fibrils (collagens I, II, III, V, XI, XXIV, and XXVII), non-fibrillar networks (collagen IV), and lattices (collagens VIII and X). Other subfamilies include fibril-associated collagens (collagens VII, IX, XII, XIV, XVI, XIX, XX, XXI, and XXII) and transmembranous collagens (collagen XIII, XVII, XXIII, and XXV).

Proteoglycans

Proteoglycans (PGs) consist of a diverse group of core proteins to which sulfated glycosaminoglycan (GAG) side chains are covalently linked. The GAG chains can be classified as keratin sulfate, chondroitin sulfate (CS), dermatan sulfate, and heparan sulfate (HS; Bulow and Hobert 2006). PGs can be secreted or cell-surface bound and serve diverse functions including ECM assembly and mediating cell adhesion and motility. PGs can be generally classified according to the major GAG chains they carry. For example, perlecan is classified as HSPG but may also carry a CS chain, especially when expressed in cartilage in which the CS may modulate FGF signaling (Smith et al. 2007a).

Basement membrane, laminin, and collagen IV

Basement membrane (BM) is a specialized ECM comprising laminins and collagen IV networks as central structural components, and nidogens and PGs. It is present in many tissues and serves as a barrier and structural support. Diversity of BM structure is partly derived from the large numbers of differentially expressed isoforms of laminins. Laminin isoforms are a family of 15 multidomain heterotrimeric glycoproteins, each assembled from a combination of five α, three β, and three γ chains (Nguyen and Senior 2006). The nomenclature for the laminins is based on chain numbers, e.g., laminin composed of α3β3γ2, formerly known as laminin-5, is now called laminin-332 (Aumailley et al. 2005). Collagen IV is a heterotrimeric protomer of three isoforms with the “classic” isoform α12α2(IV) present in BM of most tissues (Yurchenco et al. 2004; Khoshnoodi et al. 2008).

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Tsang, K.Y., Cheung, M.C.H., Chan, D. et al. The developmental roles of the extracellular matrix: beyond structure to regulation. Cell Tissue Res 339, 93 (2010). https://doi.org/10.1007/s00441-009-0893-8

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Keywords

  • Extracellular matrix
  • Development
  • Morphogenesis
  • Organogenesis
  • Mouse model