Single nucleus transcriptomes from post-synaptic targets of the corticospinal tract with respect to laterality.

The spinal cord receives inputs from the cortex via corticospinal neurons (CSNs). While predominantly a contralateral projection, a less-investigated minority of its axons terminate in the ipsilateral spinal cord. We analyzed the spatial and molecular properties of these ipsilateral axons and their post-synaptic targets in mice and found they project primarily to the ventral horn, including directly to motor neurons. Barcode-based reconstruction of the ipsilateral axons revealed a class of primarily bilaterally-projecting CSNs with a distinct cortical distribution. The molecular properties of these ipsilaterally-projecting CSNs (IP-CSNs) are strikingly similar to the previously described molecular signature of embryonic-like regenerating CSNs. Finally, we show that IP-CSNs are spontaneously regenerative after spinal cord injury. The discovery of a class of spontaneously regenerative CSNs may prove valuable to the study of spinal cord injury. Additionally, this work suggests that the retention of juvenile-like characteristics may be a widespread phenomenon in adult nervous systems. This data is Smart-seq3 transcriptomic data from single nuclei of the post-synaptic targets of the corticospinal tract, as determined by AAV1-Cre monosynaptic tracing. AAV1-Cre was injected into the caudal forelimb area of the mouse motor cortices, driving nuclear sfGFP fluorescence in post-synaptic neurons in the spinal cord. These nuclei were sorted via FACS and sequenced using Smart-Seq3.