The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling
Autor: | Harish N. Vasudevan, Audrey K. O’Neill, Philippe Soriano, Jeffrey O. Bush, Ace E. Lewis |
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Rok vydání: | 2013 |
Předmět: |
Fluorescent Antibody Technique
Medical and Health Sciences Dopaminergic neurons Transgenic Midbrain Neural crest Craniofacial Mice 0302 clinical medicine Mesencephalon WNT1 In Situ Hybridization 0303 health sciences Blotting Reverse Transcriptase Polymerase Chain Reaction Neurogenesis Wnt signaling pathway Biological Sciences Cell biology Phenotype Neural Crest embryonic structures Stem Cell Research - Nonembryonic - Non-Human Wnt1-Cre Western Signal Transduction Genetically modified mouse animal structures Genotype Transgene Blotting Western Mice Transgenic Wnt1 Protein Biology Real-Time Polymerase Chain Reaction Article 03 medical and health sciences Genetics Animals Molecular Biology 030304 developmental biology DNA Primers Integrases Neurosciences Cell Biology Stem Cell Research Molecular biology Wnt signaling nervous system Bromodeoxyuridine Ectopic expression 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | Developmental biology, vol 379, iss 2 |
ISSN: | 1095-564X |
Popis: | The Wnt1-Cre transgenic mouse line is extensively used in the study of the development of the neural crest and its derivatives and the midbrain. The Wnt1 gene has important developmental roles in formation of the midbrain–hindbrain boundary, regulation of midbrain size, and neurogenesis of ventral midbrain dopaminergic (mDA) neurons. Here, we report that Wnt1-Cre transgenic mice exhibit phenotypes in multiple aspects of midbrain development. Significant expansion of the midbrain and increased proliferation in the developing inferior colliculus is associated with ectopic expression of Wnt1. Marked elevation of Wnt1 expression in the ventral midbrain is correlated with disruption of the differentiation program of ventral mDA neurons. We find that these phenotypes can be attributed to ectopic expression of Wnt1 from the Wnt1-Cre transgene leading to the ectopic activation of canonical Wnt/β-catenin signaling. Since these caveats could complicate the utility of Wnt1-Cre in some developmental circumstances, we report a new Wnt1-Cre2 transgenic mouse line that can serve the same purposes as the original without the associated phenotypic complications. These studies reveal an important caveat to a widely-used reagent, provide an improved version of this reagent, and indicate that the original Wnt1-Cre transgenic mouse line may be useful as a gain of function model for interrogating Wnt signaling mechanisms in multiple aspects of midbrain development. |
Databáze: | OpenAIRE |
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