A function for a newly identified ncRNA, TUG1, has been established. TUG1 is necessary for the proper formation of photoreceptors in the developing rodent retina.
The homeodomain transcription factor Chx10 is one of the earliest markers of the developing retina. It is required for retinal progenitor cell proliferation as well as formation of bipolar cells, a type of retinal interneuron. orJ (ocular retardation) mice, which are Chx10 null mutants, are microphthalmic and show expanded and abnormal peripheral structures, including the ciliary body. We show here, in a mixed genetic background, the progressive appearance of pigmented cells in the neural retina, concomitant with loss of expression of retinal markers. Fate mapping analysis using a multifunctional Chx10 BAC reporter mouse revealed this process to be direct transdifferentiation of retinal cells into pigmented cells. Microarray and in situ hybridization analyses revealed a complex program underlying the transdifferentiation. This program involved the expansion of expression of genes normally found only in the periphery into central regions of the eye. These genes included a transcription factor controlling pigmentation, Mitf, and the related factor Tfec(Tcfec – Mouse Genome Informatics), which can activate a melanogenic gene expression program. Misexpression of Chx10 in the developing retinal pigmented epithelium (RPE) caused downregulation of Mitf, Tfec, and associated pigment markers, leading to a nonpigmented RPE. These data link Chx10 and Mitf to maintenance of the neural retina and RPE fates respectively. Further, they suggest a new role for Chx10 in maintenance of compartment boundaries in the peripheral retina.
Neurotransmitter receptors are central to communication at synapses. Many components of the machinery for neurotransmission are present prior to synapse formation, suggesting a developmental role. Here, evidence is presented that signaling through glycine receptor alpha2 (GlyRalpha2) and GABA(A) receptors plays a role in photoreceptor development in the vertebrate retina. The signaling is likely mediated by taurine, which is present at high levels throughout the developing central nervous system (CNS). Taurine potentiates the production of rod photoreceptors, and this induction is inhibited by strychnine, an antagonist of glycine receptors, and bicuculline, an antagonist of GABA receptors. Gain-of-function experiments showed that signaling through GlyRalpha2 induced exit from mitosis and an increase in rod photoreceptors. Furthermore, targeted knockdown of GlyRalpha2 decreased the number of photoreceptors while increasing the number of other retinal cell types. These data support a previously undescribed role for these ligand-gated ion channels during the early stages of CNS development.
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