Motor neurons involved in fine motor control are labeled by tracing Atoh1-lineage neurons in the spinal cord

Abstract

Motor neurons (MNs) innervating the digit muscles of the intrinsic hand and foot (IH and IF) control fine motor movements. Previous studies suggest that the IH and IF MN pools have a unique developmental history in comparison to limb MN pools. Consistent with having this unique development, we find that the IH and IF MN pools are labeled postnatally using a CRE knock-in mouse line of Atoh1, a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, while limb-innervating MN pools are not. Approximately 60% of the IH and IF MN pools are labeled and are a mixture of alpha and gamma-MNs. In addition, because Atoh1 is known developmentally to specify many cerebellar-projecting neurons, we tested the hypothesis that IH and IF MNs can send axon collaterals to the cerebellum as a mechanism of corollary discharge. Using intersectional genetic, viral labeling, and retrograde labeling strategies, we were unable to provide evidence in support of this idea. As a secondary finding of our viral labeling experiments, we report here that injection of both AAV and Lentiviruses in the periphery can cross the blood-brain barrier to infect Purkinje cells within the central nervous system. Altogether, though, we find that labeling of the IH and IF motor neurons using the Atoh1 CRE knock-in mouse suggests that IH and IF MNs have a unique developmental history and that this mouse strain might be a useful tool to target these specific sets of neurons allowing for functional studies of fine motor control. Significance StatementMotor neurons (MNs) of the intrinsic hand and foot (IH and IF) are labeled postnatally using a CRE knock-in mouse line of the basic helix-loop-helix (bHLH) transcription factor Atoh1 indicating a unique developmental history. We tested whether IH and IF MNs send axon collaterals rostrally to the cerebellum as a mechanism of direct corollary discharge from MNs, but the question remains unresolved. As a resource for the community, we report that injection of both AAV and Lentiviruses in the periphery can cross the blood-brain barrier and infect Purkinje cells within the central nervous system.