Expression of Shc family protein (Shc/ShcA, SCK/ShcB and N-Shc/ShcC) and Grb2 mRNAs in the hypoglossal motoneurons after axotomy was examined by in situ hybridization. In normal hypoglossal motor neurons, N-Shc mRNA was expressed predominantly, whereas the Shc mRNA level is very low. Rat hypoglossal nerve injury reversed the expressions of these two molecules in hypoglossal motoneurons. Shc mRNA expression was up-regulated markedly whereas N-Shc was down-regulated after nerve injury. Expression levels of SCK, another Shc family member, and Grb2 were unaffected by nerve injury. These results suggest that, whereas the N-Shc-mediated pathway dominates under normal conditions, an alternative Shc-mediated pathway is utilized in the event of nerve injury. By changing the expression of the Shc family members, the signaling pathway can be altered and various responses induced for nerve regeneration.
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