Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

The coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate.

Progress has been made deciphering the gene regulatory programmes that are responsible for this process; however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms.

the analysis highlighted a previously underappreciated temporal component to the mechanisms that generate neuronal diversity, and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes.

Neuronal circuits in the spinal cord receive and process incoming sensory information from the periphery, and control motor output to coordinate movement and locomotion

Although aspects of the gene regulatory network that controls neural tube patterning and neuronal differentiation have been characterised, there remain substantial gaps in our knowledge. It is unclear whether the complete catalogue of transcriptional regulators that define cell types has been established. Whether there are features in common between the mechanisms that promote the differentiation of distinct neuronal subtypes is not known. Similarly, the alterations in gene expression that accompany temporal changes in progenitor competence and cell type generation are poorly documented.

Although much progress has been made to reverse engineer the gene regulatory network that is responsible for pattern formation and cell fate specification in the neural tube […], it remains incomplete.

Analysis of the single cell transcriptome dataset revealed a set of gene expression modules that is activated synchronously at characteristic developmental timepoints in multiple neuronal classes. This raises the possibility of a coordinated temporal transcriptional programme that subdivides neuronal classes based on their time of generation. Such a mechanism would operate in parallel to the spatial patterning mechanisms and provide an opportunity to increase the molecular and functional diversity of cell types that are generated in the neural tube.

multiple secreted signalling molecules may determine into which neuronal subtypes progenitors in the spinal cord differentiate at specific timepoints.

The analysis suggests a temporal axis that contributes to the neuronal diversity that accompanies the well-characterised spatial patterning of neural progenitors.