Successful regeneration of injured neurons requires a complex molecular response that involves the expression, modification and transport of a large number of proteins. The identity of neuronal proteins responsible for the initiation of regenerative neurite outgrowth is largely unknown. Dorsal root ganglion (DRG) neurons display robust and successful regeneration following lesion of their peripheral neurite, whereas outgrowth of central neurites is weak and does not lead to functional recovery. We have utilized this differential response to gain insight in the early transcriptional events associated with successful regeneration. Surprisingly, our study shows that peripheral and central nerve crushes elicit very distinct transcriptional activation, revealing a large set of novel genes that are differentially regulated within the first 24 h after the lesion. Here we show that Ankrd1, a gene known to act as a transcriptional modulator, is involved in neurite outgrowth of a DRG neuron-derived cell line as well as in cultured adult DRG neurons. This gene, and others identified in this study, may be part of the transcriptional regulatory module that orchestrates the onset of successful regeneration. © The Authors (2007).