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
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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