Modeling the spatio-temporal network that drives patterning in the vertebrate central nervous system

In this review, we discuss the gene regulatory network underlying the patterning of the ventral neural tube during vertebrate embryogenesis. The neural tube is partitioned into domains of distinct cell fates by inductive signals along both anterior-posterior and dorsal-ventral axes. A defining feature of the dorsal-ventral patterning is the graded distribution of Sonic hedgehog (Shh), which acts as a morphogen to specify several classes of ventral neurons in a concentration-dependent fashion. These inductive signals translate into patterned expressions of transcription factors that define different neural progenitor subtypes. Progenitor boundaries are sharpened by repressive interactions between these transcription factors. The progenitor-expressed transcription factors induce another set of transcription factors that are thought to contribute to neural identities in post-mitotic neural precursors. Thus, the gene regulatory network of the ventral neural tube patterning is characterized by hierarchal expression [inductive signal → progenitor specifying factors (mitotic) → precursor specifying factors (post mitotic) → differentiated neural markers] and cross-repression between progenitor-expressed regulatory factors. Although a number of transcriptional regulators have been identified at each hierarchal level, their precise regulatory relationships are not clear. Here we discuss approaches aimed at clarifying and extending our understanding of the formation and propagation of this network.