Modeling the interplay of generic and genetic mechanisms in cleavage, blastulation, and gastrulation

Early development of multicellular organisms is marked by a rapid initial increase in their cell numbers, accompanied by spectacular morphogenetic processes leading to the gradual formation of organs of characteristic shapes. During morphogenesis, through differentiation under strict genetic control, cells become more and more specialized. Morphogenesis also requires coordinated cell movement and elaborate interactions between cells, governed by fundamental physical or generic principles. As a consequence, early development must rely on an intricate interplay of generic and genetic mechanisms. We present the results of computer simulations of the first nontrivial morphogenetic transformations in the life of multicellular organisms: initial cleavages, blastula formation, and gastrulation. The same model, which is based on the physical properties of individual cells and their interactions, describes all these processes. The genetic code determines the values of the model parameters. The model accurately reproduces the major steps of early development. It predicts that physical constraints strongly influence the timing of gastrulation. Gastrulation must occur prior to the appearance of dynamical instability, which would destabilize and eventually derail normal development. Within our model, to avoid the instability, we suddenly change the values of some of the model parameters. We interpret this change as a consequence of specific gene activity. After changing the physical characteristics of some cells, normal development resumes, and gastrulation proceeds. © 2000 Wiley‐Liss, Inc.

[1]  D. Drasdo,et al.  Buckling instabilities of one-layered growing tissues. , 2000, Physical review letters.

[2]  G. Forgacs,et al.  Surface tensions of embryonic tissues predict their mutual envelopment behavior. , 1996, Development.

[3]  Different Growth Regimes Found in a Monte Carlo Model of Growing Tissue Cell Population , 1996 .

[4]  Y. Hiramoto,et al.  Mechanical properties of the protoplasm of the sea urchin egg. I. Unfertilized egg. , 1969, Experimental cell research.

[5]  D. Beysens,et al.  Networks of Droplets Induced by Coalescence: Application to Cell Sorting , 1998 .

[6]  G F Oster,et al.  Measurements of mechanical properties of the blastula wall reveal which hypothesized mechanisms of primary invagination are physically plausible in the sea urchin Strongylocentrotus purpuratus. , 1999, Developmental biology.

[7]  L. Wolpert,et al.  An electron microscope study of the development of the blastula of the sea urchin embryo and its radial polarity. , 1963, Experimental cell research.

[8]  M. Leptin,et al.  Cell shape changes during gastrulation in Drosophila. , 1990, Development.

[9]  G. Oster,et al.  How do sea urchins invaginate? Using biomechanics to distinguish between mechanisms of primary invagination. , 1995, Development.

[10]  D Needham,et al.  Viscosity of passive human neutrophils undergoing small deformations. , 1993, Biophysical journal.

[11]  Lewis Wolpert,et al.  Principles of Development , 1997 .

[12]  J. Gurdon The generation of diversity and pattern in animal development , 1992, Cell.

[13]  Reinhard Lipowsky,et al.  The conformation of membranes , 1991, Nature.

[14]  Y Hiramoto Mechanical properties of the protoplasm of the sea urchin egg. II. Fertilized egg. , 1969, Experimental cell research.

[15]  D A Agard,et al.  Drosophila gastrulation: analysis of cell shape changes in living embryos by three-dimensional fluorescence microscopy , 2005 .

[16]  W. Helfrich Steric Interaction of Fluid Membranes in Multilayer Systems , 1978 .

[17]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[18]  K. Dan Cyto-embryology of echinoderms and amphibia. , 1960, International review of cytology.

[19]  M. Bissell,et al.  The Influence of Extracellular Matrix on Gene Expression: Is Structure the Message? , 1987, Journal of Cell Science.

[20]  N. Metropolis,et al.  Equation of State Calculations by Fast Computing Machines , 1953, Resonance.

[21]  Christopher C. Goodnow,et al.  Differential activation of transcription factors induced by Ca2+ response amplitude and duration , 1997, Nature.

[22]  J. McCaskill,et al.  Monte Carlo approach to tissue-cell populations. , 1995, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[23]  C. Ettensohn,et al.  Mechanisms of Epithelial Invagination , 1985, The Quarterly Review of Biology.

[24]  B Burnside,et al.  A mechanical model for epithelial morphogenesis , 1980, Journal of mathematical biology.

[25]  Y. Hiramoto Observations and measurements of sea urchin eggs with a centrifuge microscope , 1967, Journal of the American Veterinary Medical Association.

[26]  L. Wolpert Developmental Biology , 1968, Nature.

[27]  G. Forgacs,et al.  Viscoelastic properties of living embryonic tissues: a quantitative study. , 1998, Biophysical journal.

[28]  J. White,et al.  On the mechanisms of cytokinesis in animal cells. , 1983, Journal of theoretical biology.

[29]  P. Alberch,et al.  The mechanical basis of morphogenesis. I. Epithelial folding and invagination. , 1981, Developmental biology.