Neurons of the mouse spinal cord can be identified by any of several metrics, including what neurotransmitters they use, what cells they connect to, where they are located, and what neuroprogenitor gave rise to them. Osseward et al. generated a different metric, genetic signatures, and identified classes of local and projection neurons that were otherwise heterogeneous by other classification systems. With this focus on a cell’s genetic signature, its neurotransmitter phenotype, which is accessible by a variety of transcriptional routes, can be seen as a parallel to convergent evolution in development.
Science, this issue p. 385
Motor and sensory functions of the spinal cord are mediated by populations of cardinal neurons arising from separate progenitor lineages. However, each cardinal class is composed of multiple neuronal types with distinct molecular, anatomical, and physiological features, and there is not a unifying logic that systematically accounts for this diversity. We reasoned that the expansion of new neuronal types occurred in a stepwise manner analogous to animal speciation, and we explored this by defining transcriptomic relationships using a top-down approach. We uncovered orderly genetic tiers that sequentially divide groups of neurons by their motor-sensory, local-long range, and excitatory-inhibitory features. The genetic signatures defining neuronal projections were tied to neuronal birth date and conserved across cardinal classes. Thus, the intersection of cardinal class with projection markers provides a unifying taxonomic solution for systematically identifying distinct functional subsets.