Computer simulation of organogenesis: an approach to the analysis of shape changes in epithelial organs.

Embryonic development of epithelial organ primordia often involves changes in several parameters, such as cell height, cell width, cell volume, amount of extracellular space, and cell number. Since these changes often occur simultaneously, it becomes difficult to "separate out" the role that each plays in the developmental process. A computer program has been written that allows the shape of epithelial organs to be reproduced based upon measurements of the primordium. A developmental sequence can be simulated by changing the dimensions of the primordium based upon either measurements of the developmental stages or theoretical projections of changes. The primordium is divided into blocks representing groups of cells, based upon characteristics of the different cell groups. The program allows differences in cell height and circular and spiral curvatures of the primordium to be simulated. Analysis of the optic primordium using this method has allowed recognition of several regional changes during optic cup formation. These are sequential constriction of cell apices at the margin of the optic cup, expansion of the apical surface toward the center of the retinal disc, and spreading of the future pigmented layer. Simulation of other organs permits regions of morphogenetic activity to be identified.