The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis
Abstract
The floor plate, an essential ventral midline organizing center that produces the morphogen Shh, has distinct properties along the neuraxis. The neurogenic potential of the floor plate and its underlying mechanisms remain unknown. Using Shh as a driver for lineage analysis, we found that the mouse midbrain, but not the hindbrain, floor plate is neurogenic, giving rise to dopamine (DA) neurons. Distinct spatiotemporal Shh and Wnt expression may distinguish the neurogenetic potential of these structures. We discovered an inhibitory role for Shh: removal of Shh resulted in neurogenesis from the hindbrain midline and, conversely, high doses of Shh inhibited proliferation and DA neuron production in midbrain cultures. We found that Wnt/beta-catenin signaling is necessary and sufficient for antagonizing Shh, DA progenitor marker induction and promotion of dopaminergic neurogenesis. These findings demonstrate how the dynamic interplay of canonical Wnt/beta-catenin signaling and Shh may orchestrate floor plate neurogenesis or a lack thereof.
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“These neurons originate from the mesodiencephalic floorplate (FP), a region at the ventral midline defined by the mRNA expression of Shh+ and Foxa2+ [67–73].”
From Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches (2020) · cites this paper as [68]
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Cites
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Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism
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Identification of intrinsic determinants of midbrain dopamine neurons
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Jaeger, I. S. (2012) · Spiral (Imperial College London) · doi:10.25560/14558
Rössler, R. (2008) · University of Groningen research database (University of Groningen / Centre for Information Technology)
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Schweitzer, J. S., Song, B., & Kim, K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822229-4.00005-x
Moon, H., Kim, H., Lee, E. H., Kim, H., Kim, J. H., Jeong, H., Cheon, J., Jeong, G. R., Lee, B. D., Cho, J.-W., et al. (2026) · Advancement of science · doi:10.1002/advs.78007
Metadata
- Authors
- Joksimovic, M., Yun, B. A., Kittappa, R., Anderegg, A. M., Chang, W. W., Taketo, M. M., McKay, R. D. G., & Awatramani, R. B.
- Affiliations
- Northwestern University (US)
- National Institutes of Health (US)
- Kyoto University (JP)
- Corresponding author
- Awatramani, Rajeshwar B
- Venue
- Nature Neuroscience
- Published
- 2009-01-04
- Volume
- 12
- Issue
- 2
- Pages
- 125-131
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2144216324
- Cited by
- 213
- References
- 37
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 14 · 2016: 7 · 2015: 19 · 2014: 11 · 2013: 20 · 2012: 18
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- floor plate, midbrain, dopaminergic neurons, Sonic hedgehog, Wnt/β-catenin signaling, neurogenesis, neuronal proliferation
- MeSH terms
- Animals, Cells, Cultured, Female, Male, Mesencephalon, Nerve Tissue Proteins, Neurons, Pregnancy, Rhombencephalon, Stem Cells, Transcription Factors, Signal Transduction, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Wnt Proteins, beta Catenin, Mice, Hepatocyte Nuclear Factor 3-beta, Basic Helix-Loop-Helix Proteins, Otx Transcription Factors, Hedgehog Proteins, Stem Cell Niche, Neurogenesis, LIM-Homeodomain Proteins
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