STAT3-mediated signaling in the determination of rod photoreceptor cell fate in mouse retina
| Autor: | Hua Qin, Lixin Zhang, Ji-Ye Wei, Colin J. Barnstable, Albert B. Deisseroth, Samuel Shao Min Zhang, Pei Hui, Xin-Yuan Fu, Bing Xie |
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| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
STAT3 Transcription Factor medicine.medical_specialty genetic structures MAP Kinase Signaling System Blotting Western Ciliary neurotrophic factor Cell fate determination Leukemia Inhibitory Factor Retina Immunoenzyme Techniques Mice Pregnancy Retinal Rod Photoreceptor Cells Internal medicine medicine Animals Rod cell Ciliary Neurotrophic Factor Enzyme Inhibitors STAT3 Fluorescent Antibody Technique Indirect Flavonoids biology Interleukin-6 Cell Differentiation Cell biology DNA-Binding Proteins medicine.anatomical_structure Endocrinology Calcium-Calmodulin-Dependent Protein Kinases biology.protein Trans-Activators Female sense organs Signal transduction Mitogen-Activated Protein Kinases Leukemia inhibitory factor Cell Division Signal Transduction |
| Zdroj: | Investigative ophthalmologyvisual science. 45(7) |
| ISSN: | 0146-0404 |
| Popis: | Purpose The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina. Methods Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry. Results Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF. Conclusions These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development. |
| Databáze: | OpenAIRE |
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