Spontaneously regenerative corticospinal neurons in mice

Fait, B. W.; Cotto, B.; Murakami, T. C.; Hagemann-Jensen, M.; Zhan, H.; Freivald, C.; Turbek, I.; Gao, Y.; Yao, Z.; Way, S. W.; Zeng, H.; Tasic, B.; Steward, O.; Heintz, N.; Schmidt, E. F.

doi:10.1101/2024.09.09.612115

bioRxiv · 10.1101/2024.09.09.612115

Spontaneously regenerative corticospinal neurons in mice

Fait, B. W.·Cotto, B.·Murakami, T. C.·Hagemann-Jensen, M.·Zhan, H.·Freivald, C.·Turbek, I.·Gao, Y.·Yao, Z.·Way, S. W.·Zeng, H.·Tasic, B.·Steward, O.·Heintz, N.·Schmidt, E. F.

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Abstract

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.

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Fait, B. W., Cotto, B., Murakami, T. C., Hagemann-Jensen, M., Zhan, H., Freivald, C., Turbek, I., Gao, Y., Yao, Z., Way, S. W., Zeng, H., Tasic, B., Steward, O., Heintz, N., Schmidt, E. F.. 2024-09-12. Spontaneously regenerative corticospinal neurons in mice. https://doi.org/10.1101/2024.09.09.612115

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