Retrograde repression of growth-associated protein-43 mRNA expression in rat cortical neurons.
Corticospinal neurons support rapid growth of axons toward spinal cord targets in the perinatal period. Initial axon growth is accompanied by elevated expression of growth-associated protein-43 (GAP-43), which then declines in postnatal development. To investigate whether expression of GAP-43 mRNA is regulated by retrograde signals, we injected colchicine into the corticospinal tract to block retrograde axonal transport during a time when GAP-43 is normally declining in corticospinal neurons. Colchicine caused a prolongation of high GAP-43 mRNA expression in neurons located in layer V (but not other layers) of sensorimotor cortex. We next used osmotic minipumps to infuse soluble adult spinal cord extract into the sensorimotor cortex. This resulted in a premature downregulation of GAP-43 mRNA in identified corticospinal neurons. GAP-43 repressive activity was found in extracts of the spinal cord tissue as young as postnatal day 8. The effect of spinal cord extract in vivo was not mimicked by adult cerebellar or muscle extracts. Cultures of postnatal cortical neurons also underwent downregulation of GAP-43 mRNA when treated with spinal cord extract. Activation of cAMP signaling also repressed GAP-43 mRNA in cortical cultures, and the repressive effect of spinal cord extract was diminished by an adenyl cyclase inhibitor. Thus, GAP-43 mRNA may be downregulated late in development by a target-derived retrograde repressive factor, and this effect may be mediated by cAMP second messenger signaling.
Karimi-Abdolrezaee
Soheila
S
Cameco MS Neuroscience Research Center and Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada S7K 0M7.
Schreyer
David J
DJ
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004333:Drug Administration Routes; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry
D002457:Cell Extracts; D019922:GAP-43 Protein; D012333:RNA, Messenger; D000242:Cyclic AMP; D003078:Colchicine