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Published on: December 30, 2009
Manipulating gene activity in Wnt1-expressing precursors of neural epithelial and neural crest cells
Wei Hsu1, Anthony J Mirando, Hsiao-Man Ivy Yu
1Department of Biomedical Genetics, Center for Oral Biology, James Wilmot Cancer Center, University of Rochester Medical Center, 601 Elmwood Avenue, Box 611, Rochester, NY 14642, USA. Wei_Hsu@urmc.rochester.edu
Abstract:
Targeted gene disruption or expression often encounters lethality. Conditional approaches, permitting manipulation at desired stages, are required to overcome this problem in order to analyze gene function in later developmental processes. Wnt1 has been shown to be expressed in neural crest precursors at the dorsal midline region. However, its expression was not detected in emigrated neural crest cells, the descendants of Wnt1-expressing precursors. We have developed mouse transgenic systems to manipulate gene activity in the Wnt1-expressing precursors and their derivatives by integrating the tetracycline-dependent activation and Cre-mediated recombination methods. A new Wnt1-rtTA strain, carrying rtTA under control of Wnt1 regulatory elements, has been created for gene manipulation in a spatiotemporal-specific fashion. Together with our previously developed Wnt1-Cre;R26STOPrtTA model, these systems permit conditional gene expression and ablation in pre-migratory and/or post-migratory neural crest cells. This study demonstrated the versatility of our mouse models to achieve gene manipulation in early neural development.
Insights
Conditional gene manipulation is crucial for studying gene function during development. This study introduces novel mouse models for precise control over Wnt1 gene activity in neural crest cells, enabling functional analysis.
Area of Science:
- Developmental biology
- Genetics
- Neuroscience
Background:
- Targeted gene manipulation can cause lethality, hindering the study of gene function in later developmental stages.
- Wnt1 is expressed in neural crest precursors but not in their emigrated descendants, suggesting a need for temporal control.
Purpose of the Study:
- To develop versatile mouse transgenic systems for spatiotemporal control of gene activity.
- To enable conditional gene expression and ablation in pre-migratory and post-migratory neural crest cells.
Main Methods:
- Integration of tetracycline-dependent activation and Cre-mediated recombination.
- Development of a Wnt1-rtTA mouse strain for inducible gene manipulation.
- Utilizing a Wnt1-Cre;R26STOPrtTA model for conditional gene targeting.
Main Results:
- Successful creation of mouse models for spatiotemporal gene manipulation.
- Demonstrated ability to control gene activity in Wnt1-expressing precursors and their derivatives.
- Enabled conditional gene manipulation in both pre-migratory and post-migratory neural crest cells.
Conclusions:
- The developed mouse models offer versatile tools for studying gene function in early neural development.
- These systems overcome limitations of constitutive gene targeting in developmental studies.
- Facilitates detailed analysis of neural crest cell development and function.
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