Abstract

Young and Cepko investigated the signals involved in cell fate specification in the developing retina. They found that in retinas cultured from postnatal day 0 (P0) mice, the addition of taurine, a ligand for glycine and ionotropic γ-aminobutyric acid type A (GABA A ) receptors, stimulated rod cell production through a mechanism that could be inhibited by application of drugs that blocked glycine or GABA A receptors. Furthermore, only the application of glycine and GABA together was able to stimulate rod cell production to an extent similar to that produced by taurine application. In situ mRNA analysis indicated that glycine receptor α2 (GlyRα2) subunits and GABA α6 subunits were present in retinas from P0 mice. If GlyRα2 was overexpressed in retina isolated from E16 embryos that were cultured for 12 days in the presence of taurine, then there was an increase in rod cells, cone cells, and amacrine cells and a decrease in progenitor and Muller glial cells (identified as positive for glutamine synthetase) compared with amounts of those cell types in wild-type retinas. Evidence that taurine activation of the receptors was important for these changes in cell specification came from experiments showing that mutant forms of the GlyRα2 that could not bind taurine did not promote similar changes. In vivo treatment of P0 rat retina with RNAi to knock down GlyRα2 resulted in an increase in the number of bipolar cells and Muller glial cells and a decrease in the number of rod cells. Further studies will be needed to understand if and how the abundance of taurine, which is an amino acid derived from cysteine that can be synthesized locally or taken up from the circulation, is controlled. Rentería et al. discuss these findings. T. L. Young, C. L. Cepko, A role for ligand-gated ion channels in rod photoreceptor development. Neuron 41 , 867-879 (2004). [Online Journal] R. C. Rentería, J. Johnson, D. R. Copenhagen, Need rods? Get glycine receptors and taurine. Neuron 41 , 839-841 (2004). [Online Journal]

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