Our data suggest that CNTF remodels the transcription profile of Mller (glial) cells leading to induction of networks associated with transcription, cell cycle regulation and inflammatory response. CNTF also appears to function as an inducer of gliosis in the retina. These studies provide new insights into the biological functions of cytokines in the retina.
Ciliary neurotrophic factor induces genes associated with inflammation and gliosis in the retina: a gene profiling study of flow-sorted, Müller cells.
Specimen part, Treatment, Time
View SamplesNotch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.
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Specimen part
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