PMID- 10383634
OWN - NLM
STAT- MEDLINE
DCOM- 19990730
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 11
IP  - 7
DP  - 1999 Jul
TI  - Differential regulation of distinct phenotypic features of serotonergic neurons 
      by bone morphogenetic proteins.
PG  - 2444-52
AB  - Bone morphogenetic proteins (BMPs), growth and differentiation factor 5 (GDF5) 
      and glial cell line-derived neurotrophic factor (GDNF) are members of the 
      transforming growth factor-beta superfamily that have been implicated in tissue 
      growth and differentiation. Several BMPs are expressed in embryonic and adult 
      brain. We show now that BMP-2, -6 and -7 and GDF5 are expressed in the embryonic 
      rat hindbrain raphe. To start to define roles for BMPs in the regulation of 
      serotonergic (5-HT) neuron development, we have generated serum-free cultures of 
      5-HT neurons isolated from the embryonic (E14) rat raphe. Addition of saturating 
      concentrations (10 ng/mL) of BMP-6 and GDF5 augmented numbers of tryptophan 
      hydroxylase (TpOH) -immunoreactive neurons and cells specifically taking up 5, 
      7-dihydroxytryptamine (5,7-DHT) by about two-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 short-term treatments. Importantly, BMP-7 
      selectively induced 5, 7-DHT uptake without affecting TpOH immunoreactivity. 
      BMP-6 and -7 also promoted DNA synthesis and increased numbers of cells 
      immunoreactive for vimentin and glial fibrillary acidic protein (GFAP). 
      Pharmacological suppression of cell proliferation or glial development abolished 
      the induction of serotonergic markers by BMP-6 and -7, suggesting that BMPs act 
      indirectly by stimulating synthesis or release of glial-derived serotonergic 
      differentiation factors. Receptor bodies for the neurotrophin receptor trkB, but 
      not trkC, abolished the BMP-mediated effects on serotonergic development, 
      suggesting that the glia-derived factor is probably brain-derived neurotrophic 
      factor (BDNF) or neurotrophin-4. In support of this notion, we detected increased 
      levels of BDNF mRNA in BMP-treated cultures. Together, these data suggest both 
      distinct and overlapping roles of several BMPs in regulating 5-HT neuron 
      development.
FAU - Galter, D
AU  - Galter D
AD  - Department of Neuroanatomy, The University of Heidelberg, Germany.
FAU - Bottner, M
AU  - Bottner M
FAU - Krieglstein, K
AU  - Krieglstein K
FAU - Schomig, E
AU  - Schomig E
FAU - Unsicker, K
AU  - Unsicker K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
SB  - IM
MH  - 5,7-Dihydroxytryptamine/pharmacokinetics
MH  - Animals
MH  - Bone Morphogenetic Proteins/metabolism/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Neuroglia/physiology
MH  - Neurons/*drug effects/metabolism/*physiology
MH  - Phenotype
MH  - Raphe Nuclei/embryology
MH  - Rats
MH  - Rats, Wistar
MH  - Rhombencephalon/embryology
MH  - Serotonin/*metabolism
MH  - Stem Cells/physiology
MH  - Tryptophan Hydroxylase/pharmacokinetics
EDAT- 1999/06/26 00:00
MHDA- 1999/06/26 00:01
CRDT- 1999/06/26 00:00
PHST- 1999/06/26 00:00 [pubmed]
PHST- 1999/06/26 00:01 [medline]
PHST- 1999/06/26 00:00 [entrez]
AID - ejn667 [pii]
AID - 10.1046/j.1460-9568.1999.00667.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 1999 Jul;11(7):2444-52. doi: 10.1046/j.1460-9568.1999.00667.x.