D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.
Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators.
Lankford
K L
KL
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60201.
DeMello
F G
FG
Klein
W L
WL
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006131:Growth Inhibitors; D009024:Morphogenesis; D011954:Receptors, Dopamine / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000254:growth & development*
D018492:Dopamine Antagonists; D006131:Growth Inhibitors; D011954:Receptors, Dopamine; D005576:Colforsin; D000262:Adenylyl Cyclases; D004298:Dopamine