Neural Tube Patterning: From a Minimal Model for Rostrocaudal Patterning Towards an Integrated 3D Model

Abstract

Rostrocaudal patterning of the neural tube is a key event in vertebrate brain development. Underlying this process are morphogen gradients which specify the fate of neural progenitor cells dose-dependently, leading to the partitioning of the tube. Although this is extensively studied experimentally, an integrated view of the genetic circuitry is currently lacking. Here, we present a minimal gene regulatory model for rostrocaudal patterning, whose configuration was determined in a data-driven way, resulting in a tristable network motif. Further analysis identified the repression of hindbrain fate as promising strategy for the improvement of current protocols for the generation of dopaminergic neurons. To test our model further, we integrated it with an established model for dorsoventral patterning to simulate the steady state pattern of a physiological 3D neural tube. Simulations of elevated morphogen secretion illustrate the sensitivity of neural tube patterning to morphogen levels, implying that these are tightly regulated during development.