Abstract
ABSTRACTThe 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. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days 9.5-13.5. We confirmed that the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, 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. Together, the data offer insight into the mechanisms that are responsible for neuronal specification and provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function and disease.
Highlights
Neuronal circuits in the spinal cord receive and process incoming sensory information from the periphery, and control motor output to coordinate movement and locomotion (Goulding, 2009; Kiehn, 2016)
We have documented the transcriptional signatures of 21,465 cells that were isolated from cervical and thoracic regions of the mouse neural tube during the developmental period in which neuronal subtypes are generated
An atlas of spinal cord gene expression The number of cells that are needed to generate a comprehensive atlas of a tissue depends on multiple factors, which include the number of cell types and the molecular differences between the cell types (Shekhar et al, 2016)
Summary
Neuronal circuits in the spinal cord receive and process incoming sensory information from the periphery, and control motor output to coordinate movement and locomotion (Goulding, 2009; Kiehn, 2016). The assembly of these circuits begins on around embryonic day (e) in mouse embryos, with the generation of distinct classes of neurons from proliferating progenitor cells that are located at defined positions within the neural tube. This is accompanied by specific changes in gene expression in progenitors (Deneen et al, 2006; Kang et al, 2012; Stolt et al, 2003)
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