Elsevier

Developmental Biology

Volume 362, Issue 2, 15 February 2012, Pages 219-229
Developmental Biology

Conditional ablation of the Notch2 receptor in the ocular lens

https://doi.org/10.1016/j.ydbio.2011.11.011Get rights and content
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Abstract

Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors have not been 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, denucleation defects, and cataracts. Notch2 mutants also had persistent lens stalks as early as E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed that upon loss of Notch2, there were elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2), and Trp63 (p63) that negatively regulates Wnt signaling, plus down-regulation of Cdh1 (E-Cadherin). Removal of Notch2 also resulted in an increased proportion of fiber cells, as was found in Rbpj and Jag1 conditional mutant lenses. However, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. We found that Notch2 normally blocks lens progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.

Highlights

► Canonical Notch signaling regulates vertebrate lens growth and differentiation. ► No Notch receptor has been implicated in mouse lens development. ► Notch2 deletion causes excess fiber cells, but no loss of proliferation.► Notch2 mutants have increased apoptosis and defective cell cycle withdrawal.► Notch2 is genetically required to maintain Cdh1 and suppress Cdkn1a expression.

Keywords

Notch2
Lens fiber cell differentiation
Lens development
Jag1
p21Cip1

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