Potentiating interactions between morphogenetic protein and neurotrophic factors in developing neurons.
mRNA for bone morphogenetic protein receptor type II (BMPR-II) was mapped to different neurons in peripheral ganglia and spinal cord of the chicken embryo. The expression of this serine/threonine kinase receptor partially overlaps with that of tyrosine kinase receptors Trk and Ret. Biological activities of osteogenic protein-1 (OP-1), a documented ligand for BMPR-II, were tested in explanted embryonic chicken ganglia and dissociated ganglionic neurons. OP-1 had only a limited stimulatory effect on neuronal survival. However, OP-1 combined with either neurotrophin-3 (NT-3, a relative of nerve growth factor) or glial cell line-derived neurotrophic factor (GDNF) potentiated neuronal survival three- to fourfold. We also show that OP-1 strongly potentiates nerve fiber outgrowth from ganglia stimulated with NT-3 or GDNF. Signaling by BMPR-II in neurons may potentiate the tyrosine kinase pathway activated by NT-3 and GDNF. The data suggest that morphogenetic proteins may modulate neurotrophic activities during neuronal development and plasticity.
Bengtsson
H
H
Department of Neuroscience, Uppsala University, Biomedical Center, Sweden. henrik.bengtsson@mun.uu.se
Söderström
S
S
Kylberg
A
A
Charette
M F
MF
Ebendal
T
T
D000595:Amino Acid Sequence; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D029721:Drosophila Proteins; D004357:Drug Synergism; D005725:Ganglia, Autonomic; D017950:Ganglia, Sensory; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015513:Oncogene Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D016212:Transforming Growth Factor beta
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; C065400:oncogene protein trk; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II