Comprehensive Physiology Wiley Online Library

Regulation of Development: Differentiation and Morphogenesis

Full Article on Wiley Online Library


The sections in this article are:

1 The Cellular Processes of Determination and Differentiation
1.1 Cell Determination
1.2 Cell Differentiation
1.3 Genes Regulate Determination and Differentiation
2 The Process of Morphogenesis
2.1 Cell Adhesion
2.2 Change in Cell Shape
2.3 Localized Cell Proliferation
2.4 Localized Cell Death
3 Strategies of Development
3.1 Cell Lineage
3.2 Cell Interactions
3.3 Tissue Interactions
4 Effect of the Cellular Microenvironment on Morphogenetic Behavior
4.1 Extracellular Matrix Components
4.2 Matrix‐Associated Effectors of Cell Behavior
4.3 Biological Activities of Extracellular Matrix Components
4.4 Peptide Growth Factors
5 Reparative Responses to Injury Analogous to Developmental Processes
Figure 1. Figure 1.

Appearance of A253 salivary gland cells on plastic (left) and basement membrane matrigel (right) after 3 d.

Figure 2. Figure 2.

Appearance of human umbilical vein endothelial cells on plastic (left) and basement membrane matrigel (right) after 18 h in culture.

Figure 1.

Appearance of A253 salivary gland cells on plastic (left) and basement membrane matrigel (right) after 3 d.

Figure 2.

Appearance of human umbilical vein endothelial cells on plastic (left) and basement membrane matrigel (right) after 18 h in culture.

 1. Asch, A. S., J. Tepler, S. Silbyer, and R. L. Nachman. Cellular attachment to thrombospondin. J. Biol. Chem. 266: 1740–1747, 1991.
 2. Aumailley, M., and R. Timpl. Attachment of cells to basement membrane collagen IV. J. Cell Biol. 103: 1569–1575, 1986.
 3. Baron van Evercooren, A., H. K. Kleinman, S. Ohno, P. Marangos, J. P. Schwartz, and M. DuBois‐Dalcq. Nerve growth factor, laminin and fibronectin promote neurite outgrowth in human fetal sensory ganglia cultures. J. Neurosci. Res. 8: 179–193, 1982.
 4. Beck, K., I. Hunter, and J. Engel. Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J. 4: 148–160, 1990.
 5. Bell, E., B. Ivarsson, and C. Merrill. Production of a tissue‐like structure by construction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. U.S.A. 76: 1274–1278, 1979.
 6. Bernfield, M., R. Kokenyesi, M. Kato, M. T. Hinkes, J. Spring, R. L. Gallo, and E. J. Lose. Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. Annu. Rev. Cell Biol. 8: 365–398, 1992.
 7. Bissell, J. M., D. M. Arenson, J. J. Maker, and F. J. Roll. Support of cultured hepatocytes by a laminin rich gel. J. Clin. Invest. 79: 801–812, 1987.
 8. Bornstein, P. Thrombospondins: structure and regulation of expression. FASEB J. 6: 3290–3299, 1992.
 9. Carey, D. J., M. S. Todd, and C. M. Rafferty. Schwann cell myelination: induction by exogenous basement membrane‐like extracellular matrix. J. Cell Biol. 102: 2254–2263, 1986.
 10. Carraway, K. L., and C.A.C. Carraway. Membrane‐cytoskeleton interactions in animal cells. Biochim. Biophys. Acta. 988: 147–171, 1989.
 11. Cedar, H. DNA methylation and gene activity. Cell 53: 3–4, 1988.
 12. Chakravarti, S., M. F. Tam, and A. E. Chung. The basement membrane glycoprotein entactin promotes cell attachment and binds calcium. J. Biol. Chem. 265: 10597–10603, 1990.
 13. Chiquet‐Ehrismann, R., P. Kalla, C. A. Pearson, K. Beck, and M. Chiquet. Tenascin interferes with fibronectin action. Cell 53: 383–390, 1988.
 14. Cooper, A. R., and H. A. MacQueen. Subunits of laminin are differentially synthesized on mouse eggs and early embryos. Dev. Biol. 96: 467–471, 1983.
 15. Cunningham, B. A., J. J. Hemperly, B. A. Murray, et al. Neural cell adhesion molecule: structure, immunoglobulin‐like domains, cell surface modulation, and alternative RNA splicing. Science 236: 799–806, 1987.
 16. Dedhar, S., K. Jewell, M. Rojiani, and V. Gray. The receptor for the basement membrane glycoprotein entactin is the integrin α3/β1. J. Biol. Chem. 267: 18908–18914, 1992.
 17. Dressler, G. R., and P. Gruss. Do multigene families regulate vertebrate development? Trends Genet. 4: 214–219, 1988.
 18. Dynan, W. S. Modularity in promoters and enhancers. Cell 58: 1–4, 1989.
 19. Edelman, G. M. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu. Rev. Cell Biol. 2: 81–116, 1986.
 20. Ekblom, P., D. Vestweber, and R. Kemler. Cell‐matrix interactions and cell adhesion during development. Annu. Rev. Cell Biol. 2: 27–47, 1986.
 21. Engvall, E., D. Earwicker, T. Haaparanta, E. Ruoslahti, and J. R. Sanes. Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regulation 1: 731–740, 1990.
 22. Erickson, H. P., and M. A. Bourdon. Tenascin: an extracellular matrix protein prominent in specialized embryonic tissues and tumors. Annu. Rev. Cell Biol. 5: 71–92, 1989.
 23. Folkman, J., M. Klagsbrun, J. Sasse, M. Wadzinski, D. Ingber, and I. Vlodavsky. A heparin‐binding angiogenesis protein—basic fibroblast growth factor is stored within basement membranes. Am. J. Pathol. 130: 393–400, 1988.
 24. Friedlander, D. R., S. Hoffman, and G. M. Edelman. Functional mapping of cytotactin: proteolytic fragments active in cell‐substrate adhesion. J. Cell Biol. 107: 2329–2340, 1988.
 25. Gehring, W. J. Homeo boxes in the study of development. Science 236: 1245–1252, 1987.
 26. Gonzalez, A. M., M. Buscaglia, M. Org, and A. Bural. Distribution of basic fibroblast growth factor in basement membrane of diverse tissues. J. Cell Biol. 110: 753–765, 1990.
 27. Gospodarowicz, D., D. Delgado, and I. Vlodavsky. Permissive effect of the extracellular matrix on cell proliferation in vitro. Proc. Natl. Acad. Sci. U.S.A. 77: 4094–4098, 1980.
 28. Gossler, A., A. L. Joyner, J. Rossant, and W. C. Skarnes. Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. Science 244: 463–465, 1989.
 29. Grant, D. S., K. Tashiro, B. Segui‐Real, Y. Yamada, G. R. Martin, and H. K. Kleinman. Two different laminin domains mediate the differentiation of human endothelial cells into capillary‐like structures. Cell 58: 933–943, 1989.
 30. Hall, P. A., and F. M. Watt. Stem cells: the generation and maintenance of cellular diversity. Development 106: 619–633, 1989.
 31. Hardingham, T. E., and A. J. Fosang. Proteoglycans: many forms and many functions. FASEB J. 6: 861–870, 1992.
 32. Hauschka, P. V., T. L. Chen, and A. E. Mavrakos. Polypeptide growth factors in bone matrix. CIBA Found. Symp. 136: 207–225, 1988.
 33. Hauschka, S. D., and I. R. Konigsberg. The influence of collagen on the development of muscle colonies. Proc. Natl. Acad. Sci. U.S.A. 55: 119–126, 1966.
 34. Hay, E. D. (Ed), The Biology of Extracellular Matrix (2nd ed.). New York: Plenum Press, 1991.
 35. Kibbey, M. C., L. S. Royce, M. Dym, B. J. Baum, and H. K. Kleinman. Glandular morphogenesis of a human submandibular cell line by basement membrane components in vitro. Exp. Cell Res. 198: 343–357, 1992.
 36. Klausner, R. D., and J. B. Harford. Cis‐trans models for post‐transcriptional gene regulation. Science 246: 870–872, 1989.
 37. Klein, G., M. Lagegger, R. Timpl, and P. Ekblom. Role of laminin A chain in development of epithelial cell polarity. Cell 55: 331–341, 1988.
 38. Kleinman, H. K., J. Graf, Y. Iwamoto, G. T. Kitten, R. C. Ogle, M. Sasaka, Y. Yamada, G. R. Martin, and L. Luckinbill‐Edds. Role of basement membranes in cell differentiation. Ann. N.Y. Acad. Sci. 513: 134–145, 1987.
 39. Kleinman, H. K., R. J. Klebe, and G. R. Martin. Role of collagenous matrices in the adhesion and growth of cells. J. Cell Biol. 88: 473–485, 1981.
 40. Kleinman, H. K., L. L. Luckenbill‐Edds, F. B. Cannon, and G. Sephel. Use of extracellular matrix components for cell culture. Anal. Biochem. 166: 1–13, 1987.
 41. Kleinman, H. K., M. C. McGarvey, J. R. Hassell, V. L. Star, F. B. Cannon, G. W. Laurie, and G. R. Martin. Basement membrane complexes with biological activity. Biochemistry 25: 321–328, 1986.
 42. Krieg, T., R. Hein, A. Hamatochi, and M. Aumailley. Molecular and clinical aspects of connective tissue. Eur. J. Clin. Invest. 18: 105–123, 1988.
 43. Li, L., M. J. Aggeler, C. Halter, J. R. Hassell, and M. J. Bissell. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 84: 136–140, 1986.
 44. Martin, G. R., and R. Timpl. Laminin and other basement membrane components. Annu. Rev. Cell Biol. 3: 57–85, 1987.
 45. Mason, I. J., A. Taylor, J. G. Williams, H. Sage, and B.L.M. Hogan. Evidence from molecular cloning that SPARC, a major product of mouse embryo parietal endoderm, is related to an endothelial cell culture heat shock glycoprotein of Mr 43,000. EMBO J. 5: 1465–1472, 1986.
 46. Mecham, R. P. Receptors for laminin on mammalian cells. FASEB J. 5: 2538–2546, 1991.
 47. Mercola, M., C. D. Stiles. Growth factor superfamilies and mammalian embryogenesis. Development 102: 451–460, 1988.
 48. Murray, A. W., and M. W. Kirschner. Dominoes and clocks: the union of two views of the cell cycle. Science 246: 614–621, 1989.
 49. Neugebauer, K. M., C. J. Emmett, K. A. Venstrom, and L. F. Reichardt. Vitronectin and thrombospondin promote retinal neurite outgrowth: developmental regulation and role of integrins. Neuron 6: 345–358, 1991.
 50. O'Farrell, P. H., B. A. Edgar, D. Lakich, and C. F. Lehner. Directing cell division during development. Science 246: 635–640, 1989.
 51. Pelton, R. W., S. Nomura, H. L. Moses, and B.L.M. Hogan. Expression of transforming growth factor beta‐2 RNA during murine embryogenesis. Development 106: 759–767, 1989.
 52. Raines, E. W., T. F. Lane, M. L. Iruela‐Arispe, R. Ross, and E. H. Sage. The extracellular glycoprotein SPARC interacts with platelet‐derived growth factor (PDGF)‐AB and ‐BB and inhibits the binding of PDGF to its receptor. Proc. Natl. Acad. Sci. U.S.A. 87: 1281–1285, 1992.
 53. Rizzino, A. Transforming growth factor‐beta: multiple effects on cell differentiation and extracellular matrices. Dev. Biol. 130: 411–422, 1988.
 54. Rojkind, M., Z. Gatmaitan, S. Mackensen, M. Giambrone, P. Ponce, and L. M. Reid. Connective tissue biomatrix: its isolation and utilization for long term cultures of normal rat hepatocytes. J. Cell Biol. 87: 255–263, 1980.
 55. Ross, R. Platelet‐derived growth factor. Lancet 1: 1179–1182, 1989.
 56. Ruoslahti, E. Integrins. J. Clin. Invest. 87: 1–5, 1991.
 57. Ruoslahti, E., and Y. Yamaguchi. Proteoglycans as modulators of growth factor activities. Cell 64: 687–689, 1991.
 58. Sakamoto, N., M. Iwahana, F. G. Tanaka, and Y. Osada. Inhibition of angiogenesis and tumor growth by a synthetic laminin peptide CDPGYIGSR‐NH2. Cancer Res. 51: 903–906, 1991.
 59. Sakazuchi, K., M. Yanagishita, Y. Takeuchi, and G. D. Aurbach. Identification of heparan sulfate proteoglycan as a high affinity receptor for acidic fibroblast growth factor (aFGF) in a parathyroid cell line. J. Cell Biol. 266: 7270–7278, 1991.
 60. Schittny, J. C., R. Timpl, and J. Engel. High resolution immunoelectron microscope localization of functional domains of laminin, nidogen, and heparan sulfate proteoglycan in epithelial basement membrane of mouse cornea reveals different topological orientations. J. Cell Biol. 107: 1599–1610, 1988.
 61. Schule, R., M. Muller, C. Kaltschmidt, R. Renkawitz. Many transcription factors interact synergistically with steroid receptors. Science 242: 1418–1420, 1988.
 62. Senior, R. M., H. D. Gresham, G. L. Griffin, E. J. Brown, and A. E. Chung. Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its arg‐gly‐asp (RGD) domain and the leukocyte response integrin. J. Clin. Invest. 90: 2251–2257, 1992.
 63. Slack, J.M.W. Peptide regulatory factors in embryonic development. Lancet 1: 1312–1315, 1989.
 64. Sweeney, T. M., M. C. Kibbey, M. Zain, R. Fridman, and H. K. Kleinman. Basement membrane and the laminin peptide SIKVAV promote tumor growth and metastases. Cancer Metastasis. Rev. 10: 245–254, 1991.
 65. Takahashi, Y., and H. Nogawn. Branching morphogenesis of salivary epithelium in basement membrane‐like substratum separated from mesenchyme by the membrane filter. Development 111: 327–335, 1991.
 66. Takeichi, M. The cadherins: cell‐cell adhesion molecules controlling animal morphogenesis. Development 102: 639–655, 1988.
 67. Thomas, K. A. Fibroblast growth factors. FASEB J. 1: 434–440, 1987.
 68. Thompson, J. S. Basement membrane components stimulate epithelialization of intestinal defects in vivo. Cell Tissue Kinet. 23: 443–451, 1990.
 69. Tomasini, B. R., and D. F. Mosher. Thrombospondin Prog. Hemost. Thromb. 10: 269–305, 1991.
 70. Tuszynski, G. P., V. L. Rothman, M. Papole, B. Hamilton, and J. Eyal. Identification and characterization of a tumor cell receptor for CSVTCG, a thrombospondin adhesive domain. J. Cell Biol. 120: 513–521, 1993.
 71. Van Der Rest, M., and R. Garrone. Collagen family of proteins. FASEB J. 5: 2814–2823, 1991.
 72. Vlodavsky, I., R. Bar‐Shavit, G. Korner, and Z. Tuks. Extracellular matrix bound growth factors, enzymes and plasma proteins. In: Molecular and Cellular Aspects of Basement Membranes, edited by D. H. Rohrbach and R. Timpl Orlando, FL: Academic Press, 1993 p 327–343, 1993.
 73. Vlodavsky, I., R. Ishai‐Michaeli, P. Bashkin, G. Korner, and R. Bar‐Shavit. Heparan sulfate sequestration and release of basic fibroblast growth factor. Trends Biochem. Sci. 16: 268–271, 1991.
 74. Vos, H. L., S. Devarayalu, Y. de Vries, and P. Bornstein. Thrombospondin 3 (THBs 3), a new member of the thrombospondin gene family. J. Biol. Chem. 267: 12192–12196, 1992.
 75. Vracko, R. Significance of basal lamina for regeneratio of injured lung. Virchows Arch A Pathol. Anat. Histopathol. 355: 264–274, 1972.
 76. Vukicevic, S., H. K. Kleinman, F. Luyten, A. Roberts, and A. H. Reddi. Growth factors in reconstituted basement membrane (matrigel) regulate the network formation of MC 3T3‐E1 osteoblastic cells. Exp. Cell. Res., 202: 1–8, 1992.
 77. Wu, C., and A. E. Chung. Potential role of entactin in hemostasis. J. Biol. Chem. 266: 18802–18807, 1991.
 78. Yamada, K. M. Adhesive recognition sequences. J. Biol. Chem. 266: 128090–12812, 1991.
 79. Yamada, K., Fibronectin and other cell interactive glycoproteins. In: Cell Biology of Extracellular Matrix, edited by E. D. Hay. New York: Plenum, 1991, p 111–146.
 80. Yanagishita, M., and V. C. Hascall. Cell surface heparan sulfate proteoglycans. J. Biol. Chem. 267: 9451–9454, 1992.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Hynda K. Kleinman, Merton Bernfield. Regulation of Development: Differentiation and Morphogenesis. Compr Physiol 2011, Supplement 31: Handbook of Physiology, Cell Physiology: 843-857. First published in print 1997. doi: 10.1002/cphy.cp140122