Abstract
The molecular signals governing retinal development remain poorly understood, but some key molecules that play important roles have been identified. Activation of STAT3 by cytokines such as LIF and CNTF specifically blocks differentiation of rod photoreceptors. Here we test the hypothesis that PKC activation promotes development of rod photoreceptors by inhibiting STAT3. Explant cultures of mouse retina were used to study the effects of PKC activation on rod development. The expression of opsin, a rod specific marker, is induced at an early stage in retina explants cultured in the presence of PMA and this effect is prevented by the PKC inhibitor Go7874. Histological experiments show that there is expression of PKC beta1, but not PKC-alpha in the outer nuclear layer between E17.5 and PN5. In vitro data derived from cell lines shows that activation of PKC results in reduction of STAT3 phosphorylation. In addition, inhibition of PKC results in increase STAT3 phosphorylation. We suggest that cross talk of signals between STAT3 and PKC may determine the differentiation of rods from retinal progeitors.
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References
Altshuler D, Cepko C (1992) A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro. Development 114:947–957
Altshuler D, Lo Turco JJ, Rush J, Cepko C (1993) Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development 119:1317–1328
da Silva AG, Campello-Costa P, Linden R, Sholl-Franco A (2008) Interleukin-4 blocks proliferation of retinal progenitor cells and increases rod photoreceptor differentiation through distinct signaling pathways. J Neuroimmunol 196:82–93
Ezzeddine ZD, Yang X, DeChiara T, Yancopoulos G, Cepko CL (1997) Postmitotic cells fated to become rod photoreceptors can be respecified by CNTF treatment of the retina. Development 124:1055–1067
Hicks D, Barnstable CJ (1987) Different rhodopsin monoclonal antibodies reveal different binding patterns on developing and adult retina. J Histochem Cytochem 35:1317–1328
Levine EM, Fuhrmann S, Reh TA (2000) Soluble factors and the development of rod photoreceptors. Cell Mol Life Sci 57:224–234
Malek RL, Halvorsen SW (1999) Ciliary neurotrophic factor and phorbol ester each decrease selected STAT3 pools in neuroblastoma cells by proteasome-dependent mechanisms. Cytokine 11:192–199
Neophytou C, Vernallis AB, Smith A, Raff MC (1997) Müller-cell-derived leukaemia inhibitory factor arrests rod photoreceptor differentiation at a postmitotic pre-rod stage of development. Development 124:2345–2354
Reh TA (1992) Cellular interactions determine neuronal phenotypes in rodent retinal cultures. J Neurobiol 23:1067–1083
Rhee KD, Goureau O, Chen S, Yang XJ (2004) Cytokine-induced activation of signal transducer and activator of transcription in photoreceptor precursors regulates rod differentiation in the developing mouse retina. J Neurosci 24:9779–9788
Sparrow JR, Hicks D, Barnstable CJ (1990) Cell commitment and differentiation in explants of embryonic rat retina. Comparison to the developmental potential of dissociated retina. Dev Brain Res 51:69–84
Watanabe T, Raff MC (1990) Rod photoreceptor development in vitro: intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina. Neuron 4:461–467
Watanabe T, Raff MC (1992) Diffusible rod-promoting signals in the developing rat retina. Development 114:899–906
Yang XJ (2004) Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis. Semin Cell Dev Biol 15:91–103
Yokogami K, Wakisaka S, Avruch J, Reeves SA (2000) Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr Biol 10:47–50
Zhang SS, Liu M-G, Kano A, Zhan C, Fu X-Y, Barnstable CJ (2005) STAT3 activation in response to growth factors or cytokines participates in retina precursor proliferation. Exp Eye Res 81:103–115
Zhang SS, Wei JY, Kano R, Qin H, Zhang L, Xie B, Hui P, Deisseroth AB, Barnstable CJ, Fu XY (2004) STAT3-mediated signaling in the determination of rod photoreceptor cell fate in mouse retina. IOVS 45:2407–2412
Zhang SS, Wei J-Y, Lia C, Barnstable CJ, Fu X-Y (2003) Expression and activation of STAT proteins during mouse retina development. Exp Eye Res 76:421–431
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This work was supported by grants from the NIH and the Macular Vision Research Foundation.
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Pinzon-Guzman, C., Shaomin Zhang, S., Barnstable, C.J. (2010). Protein Kinase C Regulates Rod Photoreceptor Differentiation Through Modulation of STAT3 Signaling. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_3
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DOI: https://doi.org/10.1007/978-1-4419-1399-9_3
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