Dystrophin (Dp427) is a cytoskeletal protein defective in muscle and brain of Duchenne muscular dystrophy patients and dystrophic mdx mice. Compared to wild-type (WT), mdx mouse superior cervical ganglion (SCG) neurons show an altered pattern of peripheral target (i.e. iris, submandibular gland) innervation, suggesting impaired axon growth dynamics. To verify this, SCG neurons were axotomized and levels of tyrosine hydroxylase (TH), indicative of axon regeneration, were analyzed in the peripheral targets. Differently to WT, TH level in mdx mouse iris never recovered in the time-window examined, while that in the submandibular gland, rich in nerve growth factor (NGF), was comparable between the two genotypes. We, therefore, investigated whether axon growth alterations were consequent to reduced neuron sensitivity to NGF. SCG neurons were cultured in the presence of 5, 10, 50 or 100 ng/ml NGF and the number of principal neurites and total neuritic length were evaluated. Both parameters positively correlated to NGF levels, but they were always significantly lower for mdx mouse neurons respect to WT. Moreover, protein levels of phospho-TrkA and activated kinases downstream to NGF signaling were also reduced. Live imaging further demonstrated that mdx mouse neurites spent more time in resting or withdrawing than advancing, suggesting that lack of Dp427, which links cytoskeleton to extracellular matrix, interferes with NGF signal transduction, affecting growth cone advancement.