Abstract
Purpose: :
Test the hypothesis that a dominant mechanism of cellular pattern formation in the growing retina of goldfish, inhibitory control of homotypic cell fate decisions (Tyler et al. J Neurosci 25, 4565; 2005), is mediated by neurotransmitter signaling.
Methods: :
Adult goldfish were exposed for >30 d to an oral cocktail of drugs intended to either enhance or inhibit dopamine signaling. Enhancement of dopamine signaling was produced via exposure to exogenous dopamine (L–dopa and carbidopa). Inhibition of dopamine signaling was achieved via pharmacological block of D1–D5 receptors and the dopamine transporter (haloperidol, SCH 23390, and GBR 12909). Drug effects upon the production of cells immunopositive for tyrosine hydroxylase (TH+; i.e., putative dopaminergic neurons) were evaluated by analyzing the density of TH+ cells in retinal whole mounts.
Results: :
Longitudinal BrdU analysis indicated that neither drug exposure regimen significantly affected retinal growth per se, and there was no significant effect of drug exposure upon the density of pre–existing, differentiated TH+ cells. Exposure to drugs intended to inhibit dopamine signaling did, however, affect the production of TH+ cells: compared to controls, retinas from drug–exposed fish exhibited a significant, 1.7–fold greater density of TH+ cells produced subsequent to the initiation of drug exposure (p < 0.001). Exposure to the dopamine enhancement regimen produced a slight decrease in TH+ cell production that was not statistically significant (p = 0.2).
Conclusions: :
These results suggest a novel, feedback inhibitory function for dopamine in the control of homotypic cell fate decisions in the growing retina.
Keywords: development • differentiation • cell-cell communication