Dystrophin (Dp427) is a cytoskeletal protein defective in muscle and brain of Duchenne muscular dystrophy patients and mdx mice. We demonstrated that, compared with the wild-type (WT), innervation of muscular targets of the superior cervical ganglion (SCG) of mdx mice is dramatically reduced since P0. To unravel the question whether Dp427 played a role in early axon growth dynamics, in this study WT and mdx mice SCG neurons were axotomized to reactivate development-related mechanisms of axon elongation. Levels of tyrosine hydroxylase (enzyme for catecholamine synthesis) examined at different post-operative times in iris and submandibular gland (SG), SCG muscular and non muscular targets, respectively, decreased. However, while those in mdx mouse iris never recovered, re-innervation of SG, enriched in nerve growth factor (NGF), was similar between the two genotypes. Reduction in number and length of regenerated axons was also observed 1d after mdx mouse neuron axotomy in vitro. Moreover, neurite elongation of SCG neurons grown with 5, 10, 50 or 100 ng/ml NGF was always significantly lower in mdx mouse cultures respect to WT. Accordingly, levels of phosphorylated TrkA and kinases downstream to NGF signaling were also significantly reduced. Our data suggest that lack of Dp427, which mediates cytoskeleton-extracellular matrix linkage, may interfere with NGF-associated signal transduction, affecting axon growth and regeneration, both in vivo and in vitro. Grants: MIUR, ASI