Molecular models of early neural development

Kerszberg, M., and Changeux, J.-P. (2003). In: Van Ooyen, A., ed. Modeling Neural Development. Cambridge, MA: MIT Press, pp. 1-26.

Abstract

During morphogenesis, boundaries are first established among cellular territories characterized by persistent differences in gene transcription; meanwhile and afterwards, cell division and movement generate embryonic form. In this chapter we present mathematical and computer models for the control of gene transcription during development.

In the context of the developing muscle fibre, we first show how a single transcription factor, diffusing among nuclei and acting nonlinearly on nuclear transcriptional switches, suffices to create a sharp transcription boundary. We then study the case where several transcription factors are present, as in Drosophila syncytial blastoderm, and show that oligomerization of transcription factors creates combinatorial complexity, resulting in the sharp specification of multiple territories, which coincide, for example, with various ranges of concentration in a morphogen gradient.

We then propose a model that describes in minimal molecular terms the early steps in the formation the central nervous system. The formalism is based on the interaction of two transcriptional switches, a membrane receptor and its ligand, and two morphogens and incorporates cell adhesion, cell division, and cell motion. It accounts for the difference between vertebrates (which possess a neural tube) and insects (which possess a neural cord) on the basis of a few determining events in a common developmental program.