The Journal of Neuroscience, March 1, 2002, 22(5):1816-1822
Retrograde Repression of Growth-Associated Protein-43 mRNA
Expression in Rat Cortical Neurons
Soheila
Karimi-Abdolrezaee and
David
J.
Schreyer
Cameco MS Neuroscience Research Center and Department of
Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada
S7K 0M7
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.
Key words:
GAP-43; corticospinal neuron; spinal cord; development; gene repression; rat; retrograde signal; in situ
hybridization
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251816-07$05.00/0