ABSTRACT
The terminalis neurons (TNs) have been described in teleost species. In zebrafish, the TNs are located in the olfactory bulb. The TNs synthesize and release gonadotropin-releasing hormone (GnRH) as one of the major neurotransmitters. The TNs project axons to many brain areas, which include the neural retina. In the retina, the TN axons synapse with dopaminergic interplexiform cells (DA-IPCs) and retinal ganglion cells (RGCs). In this research, we examine the role of GnRH and dopaminergic signaling in TN axon projection to the retina using the transgenic zebrafish Tg(GnRH-3::GFP). While the TNs developed at 34 h postfertilization (hpf), the first TN axons were not detected in the retina until 48-50 hpf, when the first DA-IPCs were differentiated. In developing embryos, inhibition of retinal GnRH signaling pathways severely interrupted the projection of TN axons to the retina. However, inhibition of retinal dopaminergic signaling produced little effect on TN axon projection. In adult retinas, inactivation of GnRH receptors disrupted the patterns of TN axon distribution, and depletion of DA-IPCs abolished the TN axons. When DA-IPCs regenerated, the TN axons reappeared. Together, the data suggest that in developing zebrafish retinas GnRH signaling is required for TN axon projection, whereas in adult retinas activation of GnRH and dopaminergic signaling transduction is required for normal distribution of the TN axons.
Subject(s)
Dopamine/metabolism , Gonadotropin-Releasing Hormone/metabolism , Neurons/cytology , Olfactory Bulb/metabolism , Retina/cytology , Signal Transduction , Animals , Animals, Genetically Modified , Axons/metabolism , Olfactory Bulb/cytology , Signal Transduction/physiology , Synapses/metabolism , ZebrafishABSTRACT
The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in vertebrate species. Previously, we identified a homolog of the Stil gene in zebrafish mutant (night blindness b, nbb), which showed neural defects in the retina (e.g. dopaminergic cell degeneration and/or lack of regeneration). In this research, we examined the roles of Stil in cell proliferation after degeneration in adult zebrafish retinas. We demonstrated that knockdown of Stil gene expression or inhibition of Sonic hedgehog (Shh) signaling transduction decreases the rate of cell proliferation. In contrast, activation of Shh signal transduction promotes cell proliferation. In nbb(+/-) retinas, inhibition of SUFU (a repressor in the Shh pathway) rescues the defects in cell proliferation due to down-regulation of Stil gene expression. The latter data suggest that Stil play a role in cell proliferation through the Shh signal transduction pathway.