Skip to main content
SpringerLink
Log in

Intermediate filament typing of the human embryonic and fetal notochord

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

In order to characterize human notochordal tissue we investigated notochords from 32 human embryos and fetuses ranging between the 5th and 13th gestational week, using immunohistochemistry to detect intermediate filament proteins cytokeratin, vimentin and desmin, the cytokeratin subtypes 7, 8, 18, 19 and 20, epithelial membrane antigen (EMA), and adhesion molecules pan-cadherin and E-cadherin. Strong immunoreactions could be demonstrated for pan-cytokeratin, but not for desmin or EMA. Staining for pan-cadherin and weak staining for E-cadherin was found on cell membranes of notochordal cells. Also it was demonstrated that notochordal cells of all developmental stages contain the cytokeratins 8, 18 and19, but not 7 or 20. Some cells in the embryonic notochord also contained some vimentin. Vimentin reactivity increased between the 8th and 13th gestational week parallel to morphological changes leading from an epithelial phenotype to the chorda reticulum which represents a mesenchymal tissue within the intervertebral disc anlagen. This coexpression reflects the epithelial-mesenchymal transformation of the notochord, which also loses E-cadherin expression during later stages. Our findings cannot elucidate a histogenetic germ layer origin of the human notochord but demonstrate its epithelial character. Thus, morphogenetic inductive processes between the human notochord and its surrounding vertebral column anlagen can be classified as epithelial-mesenchymal interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albelda SM (1993) Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Inv 68:4–17

    Google Scholar 

  • Albers K, Fuchs E (1992) The molecular biology of intermediate filament proteins. Int Rev Cytol 134:243–279

    Google Scholar 

  • Bader BL, Jahn L, Franke WW (1988) Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Europ J Cell Biol 47:300–319

    Google Scholar 

  • Balling R, Ebensperger C, Hoffmann I, Imai K, Koseki H, Mizutani Y, Wallin J (1993) The genetics of skeletal development. Ann Génét 36:56–62

    Google Scholar 

  • Behrens J (1994) Cadherins as determinants of tissue morphology and suppressors of invasion. Act Anat 149:165–169

    Google Scholar 

  • Ben-Ze'ev A (1984) Differential control of cytokeratins and vimentin synthesis by cell-cell contact and cell spreading in cultured epithelial cells. J Cell Biol 99:1424–1433

    Google Scholar 

  • Bosman FT (1993) Integrins: cell adhesives and modulators of cell function. Histochem J 25:469–477

    Google Scholar 

  • Bouropoulou V, Bosse A, Roessner A, Vollmer E, Edel G, Wusimann P, Härle A (1989) Immunohistochemical investigation of chordomas: histogenetic and differential diagnostic aspects. Curr Top Pathol 80:183–203

    Google Scholar 

  • Broers JLV, Leij L de, Klein Rot M, Haar A ter, Lane EB, Leigh IM, Wagenaar SS, Vooijs GP, Ramaekers CS (1989) Expression of intermediate filament proteins in fetal and adult human lung tissues. Differentiation 40:119–128

    Google Scholar 

  • Bronner-Fraser M (1993) Mechanisms of neural crest cell migration. BioEssays 15:221–230

    Google Scholar 

  • Burger PC, Makek M, Kleihues P (1986) Tissue polypeptide staining of the chordoma and notochordal remnants. Acta Neuropathol (Berl) 70:269–272

    Google Scholar 

  • Carlson EC (1973) Intercellular connective tissue fibrils in the notochordal epithelium of the early chick embro. Am J Anat 136:77–90

    Google Scholar 

  • Coggi G, Dell'Orto P, Braidotti P, Coggi A, Viale G (1989) Coexpression of intermediate filaments in normal and neoplastic human tissues: a reappraisal. Ultrastruct Pathol 13:501–514

    Google Scholar 

  • Erickson CA, Perris R (1993) The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest. Dev Biol 159:60–74

    Google Scholar 

  • Erickson CA, Tucker RP, Edwards BF (1987) Changes in the distribution of intermediate-filament types in Japanese quail embryos during morphogenesis. Differentiation 34:88–97

    Google Scholar 

  • Franke WW, Grund C, Kuhn C, Jackson BW, Ilmensee K (1982) Formation of cytoskeletal elements during mouse embryogenesis. III. Primary mesenchymal cells and the first appearance of vimentin filaments. Differentiation 23:43–59

    Google Scholar 

  • Fuchs E, Weber K (1994) Intermediate filaments: structure, dynamics, function and disease. Annu Rev Biochem 63:345–382

    Google Scholar 

  • Geiger B, Ayalon O (1992) Cadherins. Ann Rev Cell Biol 8:307–332

    Google Scholar 

  • Geiger B, Volberg T, Ginsberg D, Bitzur S, Sabanay J, Hynes RO (1991) Broad spectrum of pan-cadherin antibodies, reactive with the C-terminal 24 amino acid residues of N-Cadherins. J Cell Sci 97:607–614

    Google Scholar 

  • Godsave SF, Anderton BH, Wlie CC (1986) The appearance and distribution of intermediate filament proteins during differentiation of the central nervous system, skin and notochord of Xenopus laevis. J Embryol Exp Morphol 97:201–223

    Google Scholar 

  • Götz W, Osmers R, Herken R (1995) Localization of extracellular matrix components in the embryonic human notochord and axial mesenchyme. J Anat (in press)

  • Goldman RD, Steinert PM (1990) Cellular and molecular biology of intermediate filaments. Plenum Press, New York London

    Google Scholar 

  • Hall BK (1977) Chondrogenesis of the somitic mesoderm. Adv Anat Embryol Cell Biol 53:4–53

    Google Scholar 

  • Hay ED (1991) Collagen and other matrix glycoproteins in embryogenesis. In: Hay ED (ed) Cell biology of the extracellular matrix, 2nd edn. Plenum Press, New York London, pp 419–462

    Google Scholar 

  • Herrmann H, Fouquet B, Franke WW (1989) Expression of intermediate filament proteins during development of Xenopus laevis. I. cDNA clones encoding different forms of vimentin. Development 105:279–298

    Google Scholar 

  • Heyderman E, Strudley J, Powell G, Richardson TC, Cordell JC, Mason DY (1985) A new monoclonal antibody to epithelial membrane antigen (EMA)-E29. Comparison of its immunocytochemical reactivity with polyclonal ant-EMA antibodies and with another monoclonal antibody, HMFG-2. Br J Cancer 52:355–361

    Google Scholar 

  • Jurand A (1962) The development of the notochord in chick embryos. J Embryol Exp Morphol 10:602–621

    Google Scholar 

  • Jurand A (1974) Some aspects of the development of the notochord in mouse embryos. J Embrol Exp Morphol 32:1–33

    Google Scholar 

  • Karsten U, Papsdorf G, Roloff G, Stolley P, Abel H, Walther I, Weiss H (1985) Monoclonal anti-cytokeratin antibody from a hybridoma clone generated by electrofusion. Eur J Cancer Clin Oncol 21:733–740

    Google Scholar 

  • Kasper M (1992) Cytokeratins in intracranial and intraspinal tissues. Adv Anat Embryol Cell Biol 126:1–82

    Google Scholar 

  • Kasper M, Stosiek P (1990) The expression of vimentin in epithelial cells from human nasal mucosa. Eur Arch Otorhinolaryngol 248:53–56

    Google Scholar 

  • Kasper M, Karsten U, Stosiek P, Moll R (1989) Distribution of intermediate-filament proteins in the human enamel organ: unusual complex pattern of coexpression of cytokeratin polypeptides and vimentin. Differentiation 40:207–214

    Google Scholar 

  • Koseki H, Wallin J, Wilting J, Mizutani Y, Kispert A, Ebensperger C, Herrmann BG, Christ B, Balling R (1993) A role for Pax-1 as a mediator of notochordal signals during the dorsoventral specification of vertebrae. Development 119:649–660

    Google Scholar 

  • Koskull H von, Virtanen I (1987) Induction of cytokeratin expression in human mesenchymal cells. J Cell Physiol 133:321–329

    Google Scholar 

  • Krech R, Loy V, Iglesias JR, Gerdes J, Stein H (1987) Immunhistologische Charakterisierung von Chordomen. Pathologe 8:207–212

    Google Scholar 

  • Kuruc N, Franke WW (1988) Transient coexpression of desmin and cytokeratins 8 and 18 in developing myocardial cells of some vertebrate species. Differentiation 38:177–193

    Google Scholar 

  • Lane EB (1993) Keratins. In: Royce PM, Steinmann B (eds) Connective tissue and its heritable disorders. Molecular, genetic, and medical aspects. Wiley-Liss, New York Chichester Brisbane, pp 237–248

    Google Scholar 

  • Larsen WJ (1993) Human Embryology. Churchill Livingstone, Edinburgh, London

    Google Scholar 

  • Laucrova L, Kovarik J, Bartek J, Rejthar A, Vojtesek B (1988) Novel monoclonal antibodies defining epitope of human cytokeratin 18 molecule. Hybridoma 7:495–504

    Google Scholar 

  • Makin C, Babrov LG, Bodmer WF (1984) Monoclonal antibody to cytokeratin for use in routine histopathology. J Clin Pathol 37:975–983

    Google Scholar 

  • Markl J (1991) Cytokeratins in mesenchymal cells: impact on functional concepts of the diversity of intermediate filament proteins. J Cell Sci 98:261–164

    Google Scholar 

  • Miettinen M (1993) Keratin immunohistochemistry: update of applications and pitfalls. Pathol Annu 28:113–143

    Google Scholar 

  • Minor RR (1973) Somite chondrogenesis. A structural analysis. J Cell Biol 56:27–50

    Google Scholar 

  • Moll R (1986) Epitheliale Tumormarker. Verh Dtsch Ges Pathol 70:28–50

    Google Scholar 

  • Moll R (1993) Cytokeratine als Differenzierungsmarker. Expressionsprofile von Epithelien und epithelialen Tumoren. Veröff Pathol 142:1–191

    Google Scholar 

  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Google Scholar 

  • Moll R, Hage C, Thoenes W (1991) Expression of intermediate filament proteins in fetal and adult human kidney: modulations of intermediate filament patterns during development and in damaged tissue. Lab Inv 65:74–86

    Google Scholar 

  • Moll R, Löwe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomas: a new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140:427–447

    Google Scholar 

  • Müller F, O'Rahilly R (1985) The first appearance of the neural tube and optic primordium in the human embryo at stage 10. Anat Embryol 172:157–169

    Google Scholar 

  • Müller F, O'Rahilly R (1987) The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12. Anat Embryol 176:413–430

    Google Scholar 

  • Murakami T, Wakamutsu E, Tamahashi N, Takahashi T (1985) The functional significance of human notochord in the development of vertebral column. An electron microscopic study. Tohoku J Exp Med 146:321–336

    Google Scholar 

  • Öbrink R (1993) Cell adhesion and cell-cell contact proteins. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix and adhesion proteins. Oxford University Press, Oxford New York Tokyo, pp 109–114

    Google Scholar 

  • Oosterwijk E, Van Muijen GNP, Oosterwijk-Wakka JC, Warnaar SO (1990) Expression of intermediate-sized filaments in developing and adult human kidney and in renal cell carcinoma. J Histochem Cytochem 38:385–392

    Google Scholar 

  • O'Rahilly R, Müller F (1987) Developmental stages in human embryos. Including a revision of streeter's “horizons” and a survey of the Carnegic collection (Carnegie Institution of Washington, Publication 637). Carnegie Institution, Washington

    Google Scholar 

  • Page M (1989) Changing patterns of cytokeratins and vimentin in the early chick embryo. Development 105:97–107

    Google Scholar 

  • Paranko J, Virtanen I (1986) Epithelial and mesenchymal cell differentiation in the fetal rat genital ducts: changes in the expression of cytokeratin and vimentin type of intermediate filaments and desmosomal plaque proteins. Dev Biol 117:135–145

    Google Scholar 

  • Petrali JP, Hinton DM, Moriaty GC, Sternberger LA (1974) The unlabeled antibody enzyme method of immunocytochemistry. J Histochem Cytochem 22:782–801

    Google Scholar 

  • Raju T, Adelman LS, Dahl D, Bignami A (1983) Localization of keratin in the notochord and in notochord-derived tumors —immunohistochemical study of rat embryo and human chordoma. Int J Dev Neurosci 1:375–382

    Google Scholar 

  • Ramaekers FCS, Feitz W, Moesker O, Schaart G, Herman C, Debruyne F, Vooijs P (1985) Antibodies to cytokeratin and vimentin in testicular tumour diagnosis. Virchows Arch [A] 408:127–142

    Google Scholar 

  • Salisbury JR, Isaacson PG (1985) Demonstration of cytokeratins and an epithelial membrane antigen in chordomas and human fetal notochord. Am J Surg Pathol 9:791–797

    Google Scholar 

  • Schaffer J (1930) Die Stützgewebe. In: Möllendorff W von (ed) Handbuch der mikroskopischen Anatomie des Menschen, Vol 2. Die Gewebe, 2nd part. Springer, Berlin, pp 1–390

    Google Scholar 

  • Sensenig EC (1949) The early development of the human vertebral column. Contrib Embryol 33:23–41

    Google Scholar 

  • Shimoyama Y, Hirohashi S, Hirano S, Noguchi M, Shimosato Y, Takeichi M, Abe O (1989) Cadherin cell adhesion molecules in human epithelial tissues and carcinomas. Cancer Res 49:2128–2133

    Google Scholar 

  • Shinohara H, Tanaka O (1988) Development of the notochord in human embryos: ultrastructural, histochemical, and immunohistochemical studies. Anat Rec 220:171–178

    Google Scholar 

  • Smedts F, Ramaekers F, Troyanovsky S, Prvszczynski M, Link M, Lane B, Leigh J, Schijf C, Voorijs P (1992) Keratin expression in cervical cancer. Am J Pathol 141:497–511

    Google Scholar 

  • Springer M (1972) Der Canalis neurentericus beim Menschen. Z Kinderchir 11:183–189

    Google Scholar 

  • Staagard M, Møllgård K (1989) The developing neuroepithelium in human embryonic and fetal brain studied with vimentin-immunocytochemistry. Anat Embryol 180:17–28

    Google Scholar 

  • Starck D (1979) Vergleichende Anatomie der Wirbeltiere auf entwicklungsbiologischer Grundlage. Vol. 2: Das Skeletsystem. Allgemeines, Skeletsubstanzen, Skelet der Wirbeltiere einschließlich Lokomotionstypen. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Steinert PM (1993) Structure, function, and dynamics of keratin intermediate filaments. J Invest Dermatol 100:729–734

    Google Scholar 

  • Stern CD (1990) Two distinct mechanisms for segmentation. Semin Dev Biol 1:109–116

    Google Scholar 

  • Stosiek P, Kasper M, Karsten U (1988) Expression of cytokeratin and vimentin in nucleus pulposus cells. Differentiation 39:78–81

    Google Scholar 

  • Takeichi M (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251:1451–1455

    Google Scholar 

  • Takeichi M (1993) Cadherins. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix and adhesion proteins. Oxford University Press, Oxford New York Tokyo, pp 116–118

    Google Scholar 

  • Taylor JR, Twomey LT (1988) The development of the human intervertebral disc. In: Ghosh P (ed) The biology of the intervertebral disc, vol 1. CRC Press, Boca Raton, pp 39–82

    Google Scholar 

  • Töndury G, Theiler K (1990) Entwicklungsgeschichte und Fehlbildungen der Wirbelsäule (Die Wirbelsäule in Forschung and Praxis, Vol 98). Hippokrates, Stuttgart

    Google Scholar 

  • Van de Klundert FAJM, Raats JMH, Bloemendal H (1993) Intermediate filaments: regulation of gene expression and assembly. Eur J Biochem 214:351–366

    Google Scholar 

  • Van Muijen GNP, Ruiter DJ, Warnaar SO (1987) Coexpression of intermediate filament polypeptides in human fetal and adult tissues. Lab Inv 57:359–369

    Google Scholar 

  • Vasan NS (1987) Somite chondrogenesis: the role of the microenvironment. Cell Diff 21:147–159

    Google Scholar 

  • Viebahn C, Lane EB, Ramaekers CS (1992) Intermediate filament protein expression and mesoderm formation in the rabbit embryo. A double-labelling immunofluorescence study. Roux's Arch Dev Biol 201:45–60

    Google Scholar 

  • Voitesek B, Staskova Z, Nenutil R, Bartkova J, Kovarik J, Rejthar A, Bartek J (1989) A panel of monoclonal antibodies to keratin no 7: characterization and value in tumor diagnosis. Neoplasma 37:333–342

    Google Scholar 

  • Walmsley R (1953) The development and growth of the intervertebral disc. Edinburgh Med J 66:341–364

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abt. Histologie, Zentrum Anatomie der Georg-August-Universität Göttingen, Kreuzbergring 36, D-37075, Göttingen, Germany

    Werner Götz & Rainer Herken

  2. Institut für Pathologie, Universitätsklinikum Carl Gustav Carus der Technischen Universität, Fetscherstrasse 74, D-01307, Dresden, Germany

    Michael Kasper

  3. Abt. Allgemeine Pathologie und Pathologische Anatomie II, Zentrum Pathologie, Universitätsklinikum, Robert-Koch-Strasse 40, D-37075, Göttingen, Germany

    Gösta Fischer

Authors
  1. Werner Götz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gösta Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rainer Herken
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Götz, W., Kasper, M., Fischer, G. et al. Intermediate filament typing of the human embryonic and fetal notochord. Cell Tissue Res 280, 455–462 (1995). https://doi.org/10.1007/BF00307819

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00307819

Key words

Search

Navigation