Dataset Information


Conditional ablation of the Notch2 receptor in the ocular lens

ABSTRACT: Notch 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. We have compared gene expression of ocular lenses of mice that are lens specific conditional mutants of Notch2 gene to that of littermate controls that had no ablation of Notch2 gene in the lens. Two lenses of each of the three conditional mutants and controls were pooled together and total RNA was harvested from embryonic day 19.5 (E19.5) lenses. Gene expression changes caused by absence of Notch2 gene in the lens were analyzed.

ORGANISM(S): Mus musculus  

SUBMITTER: Jun Zhang   Chun Y Gao  Tien T Le  Nadean L Brown  Senthil S Saravanamuthu  Radu Cojocaru  Chunqiao Liu  Radu I Cojocaru  Peggy S Zelenka  Pushpa Pandiyan 

PROVIDER: E-GEOD-31643 | ArrayExpress | 2011-12-31



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