Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons.
BACKGROUND
BMP-5 is expressed in the nervous system throughout development and into adulthood. However its effects on neural tissues are not well defined. BMP-5 is a member of the 60A subgroup of BMPs, other members of which have been shown to stimulate dendritic growth in central and peripheral neurons. We therefore examined the possibility that BMP-5 similarly enhances dendritic growth in cultured sympathetic neurons.


RESULTS
Sympathetic neurons cultured in the absence of serum or glial cells do not form dendrites; however, addition of BMP-5 causes these neurons to extend multiple dendritic processes, which is preceded by an increase in phosphorylation of the Smad-1 transcription factor. The dendrite-promoting activity of BMP-5 is significantly inhibited by the BMP antagonists noggin and follistatin and by a BMPR-IA-Fc chimeric protein. RT-PCR and immunocytochemical analyses indicate that BMP-5 mRNA and protein are expressed in the superior cervical ganglia (SCG) during times of initial growth and rapid expansion of the dendritic arbor.


CONCLUSIONS
These data suggest a role for BMP-5 in regulating dendritic growth in sympathetic neurons. The signaling pathway that mediates the dendrite-promoting activity of BMP-5 may involve binding to BMPR-IA and activation of Smad-1, and relative levels of BMP antagonists such as noggin and follistatin may modulate BMP-5 signaling. Since BMP-5 is expressed at relatively high levels not only in the developing but also the adult nervous system, these findings suggest the possibility that BMP-5 regulates dendritic morphology not only in the developing, but also the adult nervous system.
Beck
H N
HN
Division of Toxicology, Dept of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA. hbeck@jhsph.edu
Drahushuk
K
K
Jacoby
D B
DB
Higgins
D
D
Lein
P J
PJ
D000818:Animals; D055417:Bone Morphogenetic Protein 5; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D002352:Carrier Proteins; D002478:Cells, Cultured; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D038681:Follistatin / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins; D051898:Smad1 Protein; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D055417:Bone Morphogenetic Protein 5; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D038681:Follistatin; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525814:BMP5 protein, human; C000603843:BMP5 protein, rat; C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; C497399:SMAD1 protein, human; C497400:Smad1 protein, rat