Developmental regulation of the serotonergic transmitter phenotype in rostral and caudal raphe neurons by transforming growth factor-betas.
Serotonergic (5-HT) neurons of the CNS develop as two separate clusters, a rostral and a caudal group, within the brain stem raphe. We show here that the transforming growth factors -beta2 and -beta3 (TGF-beta) and the TGF-beta type II receptor are expressed in the embryonic rat raphe, when 5-HT neurons develop and differentiate. To investigate putative roles of TGF-betas in the regulation of 5-HT neuron development we have generated serum-free cultures isolated either from the rostral or the caudal embryonic rat raphe, respectively. In cultures from the caudal E14 raphe saturating concentrations (5 ng/ml) of TGF-beta2 and -beta3 augmented numbers of tryptophan hydroxylase (TpOH) -immunoreactive neurons and cells specifically taking up 5,7-dihydroxytryptamine (5,7-DHT) by about 1.7-fold over a period of 4 days. Treatment with TGF-betas also increased uptake of 3H-5HT uptake about 1.7-fold. Alterations in 5-HT neuron numbers were due to the induction of serotonergic markers rather than increased survival, as shown by the efficacy of delayed short-term treatments. Comparing rostral and caudal raphe cultures from different embryonic ages suggests that distinct effects of TGF-betas reflect the responsiveness of 5-HT neurons at different ages rather than of different origins.
Galter
D
D
Neuroanatomy, The University of Heidelberg, Germany. Dagmar.Galter@urz.uni-heidelberg.de
Böttner
M
M
Unsicker
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K
D015116:5,7-Dihydroxytryptamine / Q000493:pharmacokinetics; D029404:Activin Receptors; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011903:Raphe Nuclei / Q000196:embryology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D016895:Culture Media, Serum-Free; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat