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, despite 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 differentially regulated by GDNF treatment, including genes related to translation and to phenotypic specification and maturation. Interestingly, a set of genes related to cell adhesion, cytoskeleton and cellular morphology were consistently down-regulated by GDNF, suggesting a previously uncharacterized role for GDNF in repressing neurite growth and/or branching. This nuclear program initiated by GDNF was functionally confirmed in cultures of embryonic wild-type neurons sustained with nerve growth factor and in bax(-/-) neurons that survive in the absence of trophic support.
Linnarsson
S
S
Department of Medical Biophysics and Biochemistry, Molecular Neurobiology Unit, Scheeles väg 1, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Mikaels
A
A
Baudet
C
C
Ernfors
P
P
D000375:Aging / Q000235:genetics; D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014158:Transcription, Genetic / Q000187:drug effects; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein