Developmental origin of long-range neurons in the superficial dorsal spinal cord

The dorsal spinal cord, which is essential for somatosensory transmission, comprises a heterogeneous population of neurons with distinct axonal lengths and projection patterns. Although the developmental origin of local-circuit interneurons in the dorsal spinal cord has been well characterized, that of long-range neurons extending axons over a long distance such as supraspinal projection neurons and propriospinal neurons is largely unknown. In this study, we performed birthdate and lineage analyses of these long-range neurons in the mouse dorsal spinal cord. Unilateral injection of a retrograde neuronal tracer, cholera toxin B, into the brain or spinal cord efficiently labeled supraspinal projection neurons localized in Rexed's lamina I and the dorsolateral funiculus (DLF) and long-range propriospinal neurons localized in the DLF, all of which had ipsi- and contralaterally projecting populations. Most of these neurons were born between E9.5 and E10.5, much earlier than in the case of the neurogenesis of local-circuit neurons. Lineage analysis using an Lbx1-Cre mouse line demonstrated that most long-range neurons were derived from Lbx1-positive neuronal progenitors, except in the case of the contralaterally projecting propriospinal neurons. Characterization of their neurotransmitter identity revealed that almost all of the supraspinal projection neurons were excitatory, whereas the long-range propriospinal neurons comprised both excitatory and inhibitory populations. These results suggest that the supraspinal projection neurons were derived from the early-born dI5 progenitor domain and that the long-range propriospinal ones arose from several early-born progenitor domains.