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X-J Yang, K Rhee, O Goureau; Identification of Target Cell Types for Ciliary Neurotrophic Factor (CNTF) in the Developing Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2734.
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Purpose: Ciliary neurotrophic factor (CNTF) belongs to the IL-6 subfamily of cytokines and its signal is transmitted through a tripartite receptor consisting of the transmemebrane proteins gp130 and LIFR beta, as well as the CNTFR alpha. Although activation by CNTF-like ligands can effectively influence differentiation and survival of retinal neurons, the cellular signaling mechanism of this class of cytokines during retinal development remains poorly understood. This research focuses on identifying the signaling pathways and the target cell types of CNTF during postnatal mouse retinal development.Methods: The distribution of the CNTF receptor components and the intracellular signaling molecules in the developing retina was examined by immunohistochemistry. The activated signaling pathways and the activation kinetics were determined by using Western blot analyses. The retinal cell types responding to the CNTF signal were identified by double immunofluorescent staining of activated signaling molecules and retinal cell type markers in dissociated retinal cultures. The effects of cytokine treatment on neuronal and glial differentiation were analyzed using cell type markers on retinal monolayer and explant cultures.Results: In the early postnatal retina, CNTF can activate both the JAK-STAT and the ERK signaling pathways. The response of the retinal cells is rapid and transient, correlating to the induction of inhibitors for cytokine signaling. The CNTF receptor and intracellular signaling components, as well as the activated signaling molecules are distributed in proliferating progenitor cells and postmitotic cells. CNTF promotes Muller glial cell differentiation and inhibits rod photoreceptor differentiation mainly through JAK-STAT mediated signaling.Conclusion: CNTF may signal to both progenitor cells and differentiated cells. Supported by grants from the Research to Prevent Blindness Foundation, the March of Dimes Foundation, the Karl Kirchgessner Foundation, and NEI to X-J Yang.
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