Bone morphogenetic proteins BMP-6 and BMP-7 have differential effects on survival and neurite outgrowth of cerebellar granule cell neurons.
The bone morphogenetic proteins (BMPs) play an inductive role in the generation of cerebellar granule cells embryonically. Therefore, we chose to look at their effects on cerebellar granule cell survival and differentiation postnatally. The cells express mRNA for both BMP-6 and BMP-7, as well as for the receptors BMPRIA and BMPRII, demonstrating that the postnatal cells have the ability to form the heterodimer receptors needed to respond to BMPs. BMP-7 promotes cell survival, with a maximal effect at 10 ng/ml, whereas tenfold more BMP-6 is needed: Both were active over the course of 8 days in culture. In addition, both BMPs were able to protect the neurons against death from induced apoptosis (exposure to serum-free, low-potassium medium) or exposure to glutamate. However, only BMP-6 could stimulate neurite outgrowth, measured with a neurofilament ELISA, an effect that was seen over the first 6 days in culture. These results, taken together with others in the literature, suggest that the BMPs have strong neurotrophic effects that are both neuron specific and BMP specific.
Yabe
Takeshi
T
Neurotrophic Factors Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 4A31, Bethesda, MD 20892-4126, USA.
Samuels
Ivy
I
Schwartz
Joan P
JP
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D019610:Cytoprotection / Q000502:physiology; D018698:Glutamic Acid / Q000506:poisoning; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta
C525818:Bmp6 protein, rat; C525821:Bmp7 protein, rat; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D018698:Glutamic Acid; D052004:Bone Morphogenetic Protein Receptors