In this study, we identified increased gene expression of neurodevelopmental genes during E16 scarless healing, compared to their expression during the earliest stages of fetal scarring (E18). Previous studies have focused on the role of neurotrophins and their receptors with relation to adult healing after injury. In the adult, cutaneous sensory nervous fibers secrete neuropeptides within the skin. These neuropep-tides influence inflammation and healing in the skin. Higher numbers of nerve fibers with increased expression of neuropeptide proteins has been correlated with improved healing in nor-motrophic as compared to hypertrophic scar. Furthermore, loss of neuropeptide secretion from nerve endings in denervated tissues has been implicated in retarded wound contraction. We found a 2-3 fold increase in Neuropeptide Y Receptor type I, Synaptophysin, SNAP 25, Syntaxin 2, Neuronal calcium sensor 1 (NCS1), Neural visine-like calcium binding protein 1 (NVP1), Nerve growth factor-induced gene A (NGFI-A/EGR1), cJun related Transcription Factor (jun-D) and VGF8a in scarless wounds. This study is the first to show increased expression of these genes in response to injury in a fetal model. To our knowledge, no other studies have demonstrated an upregulation of neurodevelopmental genes during scarless healing that implicate fetal keratinocyte and fibroblast interactions.
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