Ontogeny of the spinal cord dorsal horn [scRNA-seq]

An exquisite example of form serving function is the dorsal horn of the spinal cord, the gateway to the central nervous system for sensory information from the body. Each sensory input to the dorsal horn targets a specific address within its laminated arrangement of diverse neuronal populations. However, it is not known how this organization emerges during development from an apparently homogenous pool of neural progenitors. Here, we found that both the excitatory and inhibitory cell families of the mouse dorsal horn were born in successive waves as temporal cohorts. The excitatory families then settled into a chronotopic map that transformed their birth order into the dorsal laminae. Diversification of families into refined neuron types was mediated by a dorsal-ventral progenitor gradient of Zic transcription factors. This work uncovered fundamental temporal and spatial factors that establish the cell types and structure of the spinal cord dorsal horn. Spinal cords taken from E14.5 and E16.5 mouse embryos at three axial levels were run on the 10X Chromium 3' gene expression assay. All spinal cord cells were indiscriminately collected, and neurons were selected post-sequencing for further analysis. The goals of this work were to identify hierarchical organization of dorsal horn neurons, and to use described axes of variation to uncover basic ontogenic principles.