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Tyrosinase-Cre mice for tissue-specific gene ablation in neural crest and neuroepithelial-derived tissues
Ian D Tonks1, Victor Nurcombe, Carol Paterson
1Queensland Institute of Medical Research, Herston, Queensland, Australia.
Abstract:
This study describes the derivation of two new lines of transgenic mice that express Cre recombinase under the control of tyrosinase transcriptional elements. To determine the suitability of the Tyrosinase-Cre transgene for tissue-specific gene ablation studies, a fate map of Cre expression domains was determined using the Z/AP reporter strain. It was shown that Cre-expressing cells contribute to a wide array of neural crest and neuroepithelial-derived lineages. The melanocytes of the harderian gland and eye choroid, sympathetic cephalic ganglia, leptomeninges of the telencephalon, as well as cranial nerves (V), (VII), and (IX) are derived either fully or partly from Cre-expressing cephalic crest. The cells contributing to the cranial nerves were the first to exhibit Cre expression at E10.5 as they were migrating into the branchial arches. The melanocytes, chromaffin cells of the adrenal medulla, and dorsal root ganglia are derived from trunk neural crest that either express Cre or were derived from Cre-expressing precursors. An array of brain tissue including the basal forebrain, hippocampus, olfactory bulb, and the granule cell layer of the lateral cerebellum, as well as the retinal pigmented epithelium and glia of the optic nerve originate from Cre-expressing neuroepithelial cells.
Insights
This study introduces new transgenic mice expressing Cre recombinase under tyrosinase control. These mice enable precise gene ablation in neural crest and neuroepithelial cells for developmental studies.
Area of Science:
- Developmental Biology
- Genetics
- Neuroscience
Background:
- Understanding gene function relies on precise genetic manipulation tools.
- Transgenic mouse models are crucial for studying complex biological processes.
- Tyrosinase transcriptional elements offer a potential regulatory mechanism for targeted gene expression.
Purpose of the Study:
- To derive and characterize new transgenic mouse lines expressing Cre recombinase under tyrosinase promoter control.
- To assess the utility of the Tyrosinase-Cre transgene for tissue-specific gene ablation.
- To create a detailed fate map of Cre expression domains within these models.
Main Methods:
- Generation of two novel transgenic mouse lines expressing Cre recombinase.
- Utilizing the Z/AP reporter strain to visualize and map Cre-expressing cell lineages.
- Embryonic analysis at E10.5 to track early Cre expression and cell migration patterns.
Main Results:
- Cre-expressing cells contribute to diverse neural crest and neuroepithelial lineages.
- Identified contributions to melanocytes, cranial nerves (V, VII, IX), sympathetic ganglia, and brain regions (hippocampus, olfactory bulb).
- Demonstrated early Cre expression in migrating cephalic crest cells and trunk neural crest derivatives.
Conclusions:
- The Tyrosinase-Cre mouse line is a valuable tool for studying gene function in neural crest and neuroepithelial derivatives.
- This model facilitates targeted gene ablation in various tissues, including the brain, sensory organs, and peripheral nervous system.
- The study provides a comprehensive fate map, aiding future research in developmental neurobiology and craniofacial development.
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