Neurons regulate Schwann cell genes by diffusible molecules.
Successful peripheral nerve regeneration and functional recovery require the reestablishment of the neuron-Schwann cell relationship in the regenerating rat sciatic nerve, neurons differentially regulate Schwann cell genes. The message for the low-affinity NGF receptor, p75NGFR, is induced in Schwann cells distal to the injury and is repressed as regenerating axons make contact with these cells. The inverse is true for mRNA of the myelin gene P0; expression decreases distal to injury and increases as new axons contact Schwann cells and a program of myelination is initiated. Using an in vitro co-culture paradigm in which primary neurons and adult Schwann cells are separated by a microporous membrane, we show that axon contact is not an absolute requirement for neuronal regulation of Schwann cell genes. In this system neurons but not other cell types, repress the expression of Schwann cell p75NGFR while inducing the expression of the POU domain transcription factor, suppressed cAMP inducible POU, and myelin P0. These results demonstrate that regenerating axons can direct the Schwann cell genetic program from a distance through diffusible molecules.
Bolin
L M
LM
Department of Neurobiology, Stanford University School of Medicine, California 94305.
Shooter
E M
EM
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D002642:Chick Embryo; D003470:Culture Media; D046508:Culture Techniques / Q000379:methods; D004058:Diffusion; D005727:Ganglia, Spinal / Q000502:physiology / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology*; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D050816:Octamer Transcription Factor-6; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics
D003470:Culture Media; D006133:Growth Substances; D009185:Myelin Proteins; C494179:Pou3f1 protein, rat; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6