The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling
Open accessAbstract
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.
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Lineage tracing the progeny of Wnt1+ progenitors confirmed a common progenitor pool that can give rise to both epithelial and neuronal cells.
“We confirmed our hypothesis of a common progenitor pool by lineage tracing the progeny of Wnt1+ progenitors (by crossing Wnt1-CRE2 (Lewis et al., 2013) with R26R-Confetti mice (Livet et al., 2007; Snippert et al., 2010), Figure 2H,I.”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Lewis et al., 2013
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A cellular and spatial map of the choroid plexus across brain ventricles and ages
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- Authors
- Lewis, A. E., Vasudevan, H. N., O’Neill, A. K., Soriano, P., & Bush, J. O.
- Affiliations
- University of California, San Francisco (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Bush, Jeffrey O.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 379
- Issue
- 2
- Pages
- 229-234
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC3804302
- OpenAlex
- W2053699349
- Cited by
- 289
- References
- 24
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 23 · 2023: 26 · 2022: 27 · 2021: 29 · 2020: 34 · 2019: 16 · 2018: 22 · 2017: 21 · 2016: 11 · 2015: 12 · 2014: 13 · 2013: 1
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH/NIDCR (R00 DE020855, RO1 DE22363)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Wnt signaling, canonical Wnt/β-catenin pathway, midbrain development, inferior colliculus, ectopic expression, neural crest derivatives
- MeSH terms
- Animals, Bromodeoxyuridine, Fluorescent Antibody Technique, Genotype, Mesencephalon, Mice, Transgenic, Neural Crest, Phenotype, Blotting, Western, Signal Transduction, In Situ Hybridization, DNA Primers, Integrases, Reverse Transcriptase Polymerase Chain Reaction, Wnt1 Protein, Mice, Neurogenesis, Real-Time Polymerase Chain Reaction
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