INTRODUCTION: Recovery after peripheral nerve lesions depends on guiding axons back to their targets. Polysialic acid upregulation by regrowing axons has been proposed recently as necessary for this target selectivity. METHODS: We reexamined this proposition using a cross-reinnervation model whereby axons from obturator motor neurons that do not upregulate polysialic acid regenerated into the distal femoral nerve. Our aim was to assess their target selectivity between pathways to muscle and skin. RESULTS: After simple cross-repair, obturator motor neurons showed no pathway preference, but the same repair with a shortened skin pathway resulted in selective targeting of these motor neurons to muscle by a polysialic acid-independent mechanism. CONCLUSION: The intrinsic molecular differences between motor neuron pools can be overcome by manipulation of their access to different peripheral nerve pathways such that obturator motor neurons preferentially project to a terminal nerve branch to muscle despite not upregulating the expression of polysialic acid.