Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation)

Abstract

The vertebrate nervous system consists of many different neuronal cell types. Each has its own properties, axon projections and connection patterns. This diversity is established early during development and is required for the complex neuronal circuits that characterise the central nervous system. In the spinal cord, a series of events generates different neuronal subtypes, starting with the spatial patterning of neural progenitors. Extrinsic signals provide progenitors in the forming neural tube with positional identity, such that distinct types of progenitors express a unique combination of transcription factors. This transcriptional code determines neural progenitor identity. As progenitors differentiate, they generate distinct neuronal subtypes that are also characterised by a combinatorial transcriptional code. In addition to spatial patterning, other mechanisms contribute to the further diversification of differentiating neurons. Key Concepts: Secreted molecules provide positional information to neural progenitors in the developing neural tube. Progenitors at different positions in the neural tube acquire distinct identities. The identity of a progenitor is defined by the combination of transcription factors it expresses, which determines the gene expression profile of the progenitor. An interplay between extrinsic signalling and the downstream gene network produces spatially discrete switches in progenitor identity. Progenitors with distinct identities differentiate into post‐mitotic neurons with different subtype identities. The identity of a neuron is determined by the transcriptional code of its progenitor and is itself defined by a separate transcriptional code. In addition to spatial pattern, temporal changes in progenitor identity and signalling between differentiating cells increases neuronal diversity.

Development-on-chip: in vitro neural tube patterning with a microfluidic device

“…1 ). The most studied of these cues is sonic hedgehog (SHH), which is generated in notochord and floor plate cells establishing a ventral (high) to dorsal (low) concentration gradient across the neural tube ( Ribes and Briscoe, 2009 ) directing the differentiation of ventral neural progenitors ( Roelink et al, 1995 ) into highly organized domains of neural subtypes ( Bushati and Briscoe, 1994 ). An opposing gradient of bone morphogenetic protein (BMP) and other members of the transforming growth factor beta (TGFβ) superfamily of signaling molecules are simultaneously released by roof plate cells, concurrently patterning the dorsal half of the neural tube and establishing a cross-repressive boundary between the dorsal and ventral halves of the developing spinal cord ( Le Dréau et al, 2012 ).…”