Cited by 213Neurogenesis and neuroplasticity mechanismsHedgehog Signaling Pathway StudiesDevelopmental Biology and Gene Regulation

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Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

Joksimovic, Milan, Yun, Beth A, Kittappa, Raja, Anderegg, Angela M, Chang, Wendy W, Taketo, Makoto M, McKay, Ronald D G, Awatramani, Rajeshwar B·2009·Nature Neuroscience

DOI 10.1038/nn.2243

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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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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
ORCID: Taketo, Makoto M
Awatramani, Rajeshwar B
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2009-01-04
Volume: 12
Issue: 2
Pages: 125-131
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2243
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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Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

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