Developmental molecular signatures define de novo cortico-brainstem circuit for skilled forelimb movement

The brainstem has been widely recognized as a key integration and processing hub between “upper” motor centers and spinal circuits involved in execution of movements. Cortical input into the brainstem may fine-tune movement execution and support motor planning and is established by two SCPN supopulations: 1) cortico-brainstem neurons (CBN) that limit their axon extension to supraspinal levels, directly innervating brainstem nuclei, and 2) corticospinal neurons (CSN) that extend their axons into the spinal cord but additionally collateralize within the brainstem.

Classical anatomical tracing approaches are not able to distinguish CBN from CSN, since these distinct subpopulations reside interdigitated in cortex, thus precluding the investigation of the function of CBN in skilled motor movement execution and planning until now. We used a combination of transcriptomics, tracing, and imaging techniques to identify the molecular program that CBN vs. CSN at the time point of initial axon extension.