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.
Drasdo
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Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany.
Forgacs
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D000465:Algorithms; D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D003198:Computer Simulation; D005775:Gastrula / Q000502:physiology*; D008954:Models, Biological; D009010:Monte Carlo Method; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*