| Autor: |
Long, Rebecca M., Ong, Honyi, Wendy Xueyi Wang, Komirishetty, Prashanth, Areti, Aparna, Chandrasekhar, Ambika, Larouche, Matt, Lefebvre, Julie L., Zochodne, Douglas W. |
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| Zdroj: |
Journal of Neuroscience; 12/6/2023, Vol. 43 Issue 49, p8348-8366, 19p |
| Abstrakt: |
The clustered protocadherins (cPcdhs) play a critical role in the patterning of several CNS axon and dendritic arbors, through regulation of homophilic self and neighboring interactions. While not explored, primary peripheral sensory afferents that innervate the epidermis may require similar constraints to convey spatial signals with appropriate fidelity. Here, we show that members of the c-Pcdh (Pcdhc) family are expressed in both adult sensory neuron axons and in neighboring keratinocytes that have close interactions during skin reinnervation. Adult mice of both sexes were studied. Pcdhc knock-down either through small interfering RNA (siRNA) transduction or AAV-Cre recombinase transfection of adult mouse primary sensory neurons from floxed Pcdhc mice was associated with a remarkable rise in neurite outgrowth and branching. Rises in outgrowth were abrogated by Rac1 inhibition. Moreover, AAV-Cre knock-down in Pcdhc floxed neurons generated a rise in neurite self-intersections, and a robust rise in neighbor intersections or tiling, suggesting a role in sensory axon repulsion. Interestingly, preconditioned (3-d axotomy) neurons with enhanced growth had temporary declines in Pcdhc and lessened outgrowth from Pcdhc siRNA. In vivo, mice with local hindpaw skin Pcdhc knock-down by siRNA had accelerated reinnervation by new epidermal axons with greater terminal branching and reduced intra-axonal spacing. Pcdhc knock-down also had reciprocal impacts on keratinocyte density and nuclear size. Taken together, this work provides evidence for a role of Pcdhc in attenuating outgrowth of sensory axons and their interactions, with implications in how new reinnervating axons following injury fare amid skin keratinocytes that also express Pcdhc. [ABSTRACT FROM AUTHOR] |
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