| The canonical role for neurotransmitters and their receptors in mature neurons is to mediate excitatory or inhibitory neurotransmission. However, many of these molecules are also present throughout the immature nervous system, suggesting that these factors may also play roles in development. In my thesis, I describe a role for taurine activation of glycine and GABA(A) receptors in the development of a specific cell type in the rodent retina, rod photoreceptors. Using a combination of pharmacology, retroviral misexpression techniques, and in vivo electroporation of siRNA constructs, I show that glycine and GABA(A) receptor activity mediate a rod promoting effect of taurine. In addition, I describe studies attempting to further our understanding of the signaling events that occur downstream of these receptors. In these studies, I performed a microarray screen to look for targets of taurine, glycine, GABA, and KCl signaling in primary retinal precursor cells, and then used bioinformatical approaches to identify common regulatory motifs involved in taurine signaling. Lastly, I have characterized one of the immediate taurine target genes identified in the microarray screen. This gene is a putative noncoding RNA that we are calling Taurine Upregulated Gene 1 (TUG1). I show that targeting of this gene using siRNA constructs prevents the formation of proper photoreceptor outer segments, indicating that this gene plays a role in photoreceptor development. In summary, the data presented in this thesis describe a role for taurine and ligand gated ion channel in the development of a specialized cell type in the retina, and further our understanding of the downstream signaling involved in this process. As taurine, glycine receptors and GABA(A) receptors are expressed throughout the developing nervous system in several vertebrate species, the effects of these factors observed in the retina may represent a general signaling mechanism that is involved in several regions of the developing nervous system. |
