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Requirement for Crk and CrkL during postnatal lens development
1Children's Mercy Research Institute, Children's Mercy Kansas City, Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, 64108, USA.
Abstract:
The Crk and CrkL adaptor proteins have SH2 and SH3 domains and play essential overlapping, as well as distinct, roles in many biological processes, ranging from cell structure and motility to proliferation. Conditional ablation of both Crk and CrkL in neuronal progenitor cells, using a Nestin-Cre transgene, resulted in severe defects in postnatal eye development, including progressive eye closure, lens rupture, and retinal malformation. These phenotypes were not observed in the presence of a single wild-type allele of either Crk or CrkL. We found that the lens in knockout mice started to rupture and disintegrate between postnatal days 7 and 12, although the structure of the retina was relatively well maintained. As the lens deteriorated further, the outer nuclear layer in the posterior of the retina enlarged and developed ruffles. Cre recombination occurred in the lens and retina of the knockout mice. Furthermore, the posterior lens capsule of the knockout mouse was thinner at postnatal days 0.5 and 3, suggesting that the defective lens capsule caused rupturing of the lens near the posterior pole. These results indicate that Crk and CrkL play essential overlapping roles in postnatal lens development.
Insights
Crk and CrkL adaptor proteins are crucial for eye development. Ablating both Crk and CrkL in mice caused severe postnatal eye defects, including lens rupture and retinal malformation, highlighting their essential roles.
Area of Science:
- Molecular Biology
- Developmental Biology
- Ophthalmology
Background:
- The Crk and CrkL adaptor proteins, featuring SH2 and SH3 domains, are implicated in diverse cellular functions like motility and proliferation.
- These proteins play overlapping yet distinct roles in various biological processes.
Purpose of the Study:
- To investigate the specific roles of Crk and CrkL adaptor proteins in postnatal eye development.
- To determine the consequences of ablating both Crk and CrkL in neuronal progenitor cells on ocular structures.
Main Methods:
- Conditional ablation of Crk and CrkL genes in neuronal progenitor cells using a Nestin-Cre transgene in mice.
- Histological analysis of postnatal eye development in knockout and control mice.
- Assessment of lens capsule integrity and retinal structure.
Main Results:
- Conditional knockout of both Crk and CrkL led to severe postnatal eye developmental defects, including progressive eye closure, lens rupture, and retinal malformation.
- Lens rupture and disintegration were observed between postnatal days 7-12, associated with a thinner posterior lens capsule.
- Retinal structures, particularly the outer nuclear layer, showed secondary alterations as the lens deteriorated.
Conclusions:
- Crk and CrkL adaptor proteins play essential, overlapping roles in maintaining normal postnatal lens development.
- Defects in the lens capsule appear to be a primary cause of lens rupture in the absence of Crk and CrkL.
- These findings underscore the critical function of Crk/CrkL in ocular morphogenesis.
