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.

The spinal cord contains an extraordinarily diverse population of interconnected neurons to process somatosensory information and execute movement. Studies of the embryonic spinal cord have elucidated basic principles underlying the specification of spinal cord neurons, while adult and postnatal studies have provided insight into cell type function and circuitry. However, the overarching principles that bridge molecularly defined subtypes with their connectivity, physiology, and function remain unclear. This review consolidates recent work in spinal neuron characterization, examining how molecular and spatial features of individual spinal neuron types relate to the reference points of connectivity and function. This review will focus on how spinal neuron subtypes are organized to control movement in the mouse.