A SIMPLE MOLECULAR-MODEL OF NEURULATION

A molecular model for the morphogenesis of the central nervous system is built and solved by computer. The formalism rests on molecular-biol ogical data gathered from insects and vertebrates during neural differ entiation and neuronal fate specification. Two genetic, hierarchically organized switches are introduced, one associated with neural tissue formation, and the other with neuronal specification. The model switch es evolve in time, setting up very similar ''prepatterns'' of genetic activity in both insects and vertebrates, as observed experimentally. We introduce the hypothesis that cell adhesion and motion are regulate d by the switches. If cell motion is turned on by the neural switch, t he whole neural tissue (neural plate) thickens, buckles, and folds, ul timately creating a closed neural tube (primary neurulation). When mit oses are more frequent in neural plate tissue, ingression of a neural cell mass takes place instead (secondary neurulation). If cell motions are controlled by the neuronal switch, rather than by the neural one, the differentiation of isolated neuroblasts is observed, which delami nate individually las in insect neural cord formation). The model thus displays the three major known patterns of neurogenesis; the transiti on between the vertebrate and insect cases is predicted to result from changes in genetic regulation downstream of the switch genes, and aff ecting cell adhesion and motility properties. Little is known experime ntally about the concerned pathways: their importance as a fruitful ar ea for future investigation is emphasized by our theoretical results. BioEssays 20:758-770, 1998. (C) 1998 John Wiley & Sons, Inc.