Brains emerging: On modularity and self-organisation of neural development in vivo and in vitro

Abstract

Molecular developmental biology has expanded our conceptions of gene actions, underpinning that embryonic development is not only governed by a set of specific genes, but as much by space-time conditions of its developing modules (determinate vs. regulative development; or, nature vs. nurture discussion). Typically, formation of cellular spheres, their transformation into planar epithelia, followed by tube formations and laminations are modular steps leading to the development of nervous tissues. Thereby, actions of organising centres, morphogenetic movements (in-and evaginations), inductive events between epithelia, tissue polarity reversal, widening of epithelia, and all these occurring orderly in space and time, are driving forces of emergent laminar neural tissues, e.g. the vertebrate retina. Analyses of selforganisational formation of retina-like 3D structures from dispersed cells (so-called retinal spheroids, also called retinal organoids) under defined cell culture conditions (in vitro) demonstrate that not only particular genetic networks, but-at least as important-the applied culture conditions (in vitro constraints) define phenotypes of emergent tissues. Such in vitro approaches allow assigning emerging tissue formation to ground-laying genetic networks separately from contributions by conditional constraints.