Abstract
Motor neurons (MNs) innervating the digit muscles of the intrinsic hand (IH) and intrinsic foot (IF) control fine motor movements. The ability to reproducibly label specifically IH and IF MNs in mice would be a beneficial tool for studies focused on fine motor control. To this end, we find that a CRE knock-in mouse line of Atoh1, a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, reliably expresses CRE-dependent reporter genes in ∼60% of the IH and IF MNs. We determine that CRE-dependent expression in IH and IF MNs is ectopic because an Atoh1 mouse line driving FLPo recombinase does not label these MNs although other Atoh1-lineage neurons in the intermediate spinal cord are reliably identified. Furthermore, the CRE-dependent reporter expression is enriched in the IH and IF MN pools with much sparser labeling of other limb-innervating MN pools such as the tibialis anterior (TA), gastrocnemius (GS), quadricep (Q), and adductor (Ad). Lastly, we find that ectopic reporter expression begins postnatally and labels a mixture of α and γ-MNs. Altogether, the Atoh1 CRE knock-in mouse strain might be a useful tool to explore the function and connectivity of MNs involved in fine motor control when combined with other genetic or viral strategies that can restrict labeling specifically to the IH and IF MNs. Accordingly, we provide an example of sparse labeling of IH and IF MNs using an intersectional genetic approach.
Highlights
Motor neurons (MNs) innervating the muscles in the digits of the hand allow for exquisite control of fine motor movements required for dexterous skills, such as writing or sewing
We observed using CRE-lineage tracing strategies (Atoh1Cre/1 knock-in mice crossed to tdTomato (TOM) reporter mice (R26LSL-Tom, Ai14)) (Yang et al, 2010; Madisen et al, 2010) that subsets of MNs expressing choline acetyltransferase (ChAT) were labeled in the spinal cord (Fig. 1A,B, arrows and arrowheads)
We found that labeling of the intrinsic hand (IH) and intrinsic foot (IF) MNs was sparse in the ChatIRES-flippase recombinase sequence (FLPo)/1 mouse line alone with only ;30% of the MN pool being labeled (IH, 26 6 5%, n = 2, 2:0 M:F, six half sections/n; IF, 31 6 5%, n = 3, 3:0 M:F, 4–10 half sections/n; Fig. 5A,C)
Summary
Motor neurons (MNs) innervating the muscles in the digits of the hand allow for exquisite control of fine motor movements required for dexterous skills, such as writing or sewing. Primates are known for their ability to precisely control individual digits of the hand, but skillful movements are not limited to the hand, as people born without. January/February 2021, 8(1) ENEURO.0221-20.2021 1–9 arms are able to dexterously manipulate tools with their toes (Shubin et al, 1997; Sustaita et al, 2013; DempseyJones et al, 2019). How MNs innervating the intrinsic hand (IH) and intrinsic foot (IF) muscles may differ in terms of function and connectivity compared with MNs that innervate limb muscles is unknown. IH and IF MNs have unique properties and connectivity that
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