Activin and bone morphogenetic proteins are present in perinatal sensory neuron target tissues that induce neuropeptides.
Previous studies have shown that sensory target tissues induce neuropeptides in naïve sensory neurons, and that activin and bone morphogenetic proteins (BMPs) are capable of inducing neuropeptides associated with nociception in embryonic sensory neurons in vitro. The goal of the present study was to learn if these ligands were available in native sensory neuron target tissues at correct developmental periods to play this inductive role in vivo. Sensory neurons initially contact their peripheral target tissues and begin to express neuropeptides during late embryogenesis, and we demonstrate that activin and BMPs are present in the embryo and neonate to regulate sensory neuron differentiation. Native embryonic and neonatal target tissues were analyzed by immunoblot and immunohistochemical studies using ligand-specific antibodies. Although activin was easily solubilized, BMPs were detected only after high salt extraction, suggesting that BMPs were bound to extracellular moieties and were capable of acting only locally in native tissues. One inhibitor, noggin, was present in both embryonic skin and muscle. In combination, these data suggest that neuronal differentiation is unlikely to be regulated by simple expression of ligand, but that the functional availability of ligand is a critical component confering biological activity.
Department of Neuroscience, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, Ohio 44106, USA. axh8@po.cwru.edu
Alison K
AK
Hall
Rebecca M
RM
Burke
Malini
M
Anand
Kyl J
KJ
Dinsio
D028341:Activins / Q000032:analysis*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D005727:Ganglia, Spinal / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D009132:Muscles / Q000737:chemistry / Q000196:embryology / Q000294:innervation; D009475:Neurons, Afferent / Q000737:chemistry* / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000737:chemistry / Q000196:embryology / Q000294:innervation; D016212:Transforming Growth Factor beta / Q000032:analysis
C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; C525818:Bmp6 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D009479:Neuropeptides; D016212:Transforming Growth Factor beta; D028341:Activins