Lhx2 and Lhx9 Determine Neuronal Differentiation and Compartition in the Caudal Forebrain by Regulating Wnt Signaling
Open accessAbstract
Initial axial patterning of the neural tube into forebrain, midbrain, and hindbrain primordia occurs during gastrulation. After this patterning phase, further diversification within the brain is thought to proceed largely independently in the different primordia. However, mechanisms that maintain the demarcation of brain subdivisions at later stages are poorly understood. In the alar plate of the caudal forebrain there are two principal units, the thalamus and the pretectum, each of which is a developmental compartment. Here we show that proper neuronal differentiation of the thalamus requires Lhx2 and Lhx9 function. In Lhx2/Lhx9-deficient zebrafish embryos the differentiation process is blocked and the dorsally adjacent Wnt positive epithalamus expands into the thalamus. This leads to an upregulation of Wnt signaling in the caudal forebrain. Lack of Lhx2/Lhx9 function as well as increased Wnt signaling alter the expression of the thalamus specific cell adhesion factor pcdh10b and lead subsequently to a striking anterior-posterior disorganization of the caudal forebrain. We therefore suggest that after initial neural tube patterning, neurogenesis within a brain compartment influences the integrity of the neuronal progenitor pool and border formation of a neuromeric compartment.
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Lhx2 and Lhx9 are co-expressed in thalamus and midbrain glutamatergic types, but Lhx2 is also specifically expressed in pallium IT-ET types.
“Lhx2 and Lhx9 are co-expressed in thalamus and midbrain glutamatergic types, but Lhx2 is also specifically expressed in the pallium IT–ET types108,109.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [109]
The Results section, “Fine Mapping of the Temporal and Spatial Expression of Lhx2 and Lhx9 in the Caudal Diencephalon” (page unavailable), reports Lhx2/Lhx9 co-expression in the zebrafish thalamus and places Lhx9 expression in a glutamatergic thalamic domain. It does not establish co-expression in midbrain glutamatergic types or specific Lhx2 expression in pallium IT–ET types; the Discussion mentions the pallium without identifying those cell types. (LLM, conf=0.88)
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Yao, Z., Liu, H., Xie, F., Fischer, S., Adkins, R. S., Aldridge, A. I., Ament, S. A., Bartlett, A., Behrens, M. M., Van den Berge, K., et al. (2021) · Nature · doi:10.1038/s41586-021-03500-8 · Cited by 398 · see citing works
What is the Thalamus in Zebrafish?
Mueller, T. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00064 · Cited by 207 · see citing works
An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types
Yao, Z., Liu, H., Xie, F., Fischer, S., Booeshaghi, A. S., Adkins, R. S., Aldridge, A. I., Ament, S. A., Pinto-Duarte, A., Bartlett, A., et al. (2020) · doi:10.1101/2020.02.29.970558 · Cited by 397 · see citing works
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- Authors
- Peukert, D., Weber, S., Lumsden, A., & Scholpp, S.
- Affiliations
- Karlsruhe Institute of Technology (DE)
- King's College London (GB)
- Corresponding author
- Peukert, Daniela
- Weber, Sabrina
- Lumsden, Andrew
- Scholpp, Steffen
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-13
- Volume
- 9
- Issue
- 12
- Pages
- e1001218
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC3236734
- OpenAlex
- W2067924946
- Cited by
- 118
- References
- 98
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 11
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- Repository KITopen (Karlsruhe Institute of Technology) (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- KITopen (other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Medical Research Council
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Lhx2, Lhx9, Wnt signaling, thalamus, pretectum, epithalamus, neuronal differentiation, cell adhesion, zebrafish, neural tube patterning, anterior-posterior axis
- MeSH terms
- Protocadherins, Animals, Nerve Tissue Proteins, Thalamus, Transcription Factors, Zebrafish, Signal Transduction, Cadherins, Prosencephalon, Gene Expression Regulation, Developmental, Body Patterning, Zebrafish Proteins, Wnt Proteins, Neural Tube, Neurogenesis, LIM-Homeodomain Proteins
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