Activation by GDNF of a transcriptional program repressing neurite growth in dorsal root ganglia

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of postnatal-but not embryonic-mouse dorsal root ganglion cells in vitro, des pite the fact that its receptors are expressed at both ages. To understand this difference, we have performed an oligonucleotide microarray experiment . We found that several hundred genes were regulated between embryonic and postnatal stages, and that several important classes of genes were differen tially regulated by GDNF treatment, including genes related to translation and to phenotypic specification and maturation. Interestingly, a set of gen es related to cell adhesion, cytoskeleton and cellular morphology were cons istently downregulated by GDNF, suggesting a previously uncharacterized rol e for GDNF in repressing neurite growth and/or branching. This nuclear prog ram initiated by GDNF was functionally confirmed in cultures of embryonic w ild-type neurons sustained with nerve growth factor and in bax(-/-) neurons that survive in the absence of trophic support.