Developmental trajectories of thalamic progenitors revealed by single-cell transcriptome profiling and Shh perturbation
Open accessAbstract
The thalamus is the principal information hub of the vertebrate brain, with essential roles in sensory and motor information processing, attention, and memory. The complex array of thalamic nuclei develops from a restricted pool of neural progenitors. We apply longitudinal single-cell RNA sequencing and regional abrogation of Sonic hedgehog (Shh) to map the developmental trajectories of thalamic progenitors, intermediate progenitors, and post-mitotic neurons as they coalesce into distinct thalamic nuclei. These data reveal that the complex architecture of the thalamus is established early during embryonic brain development through the coordinated action of four cell differentiation lineages derived from Shh-dependent and -independent progenitors. We systematically characterize the gene expression programs that define these thalamic lineages across time and demonstrate how their disruption upon Shh depletion causes pronounced locomotor impairment resembling infantile Parkinson's disease. These results reveal key principles of thalamic development and provide mechanistic insights into neurodevelopmental disorders resulting from thalamic dysfunction.
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Both RT and ZI neurons may have originated from the prethalamus or the zona limitans intrathalamica.
“Both RT and ZI neurons may have originated from the prethalamus or the zona limitans intrathalamica (ZLI)34–38.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [35]
The Results section on molecular identities at E18.5 identifies zona incerta (ZI) and reticular complex (RT) cell populations, while the Introduction describes the ZLI as separating the thalamus from the prethalamus. Neither passage, nor searches for RT and ZI origins, says that both populations may originate in the prethalamus or ZLI. Page numbers were not available in our copy. (LLM, conf=0.72)
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,194 · see citing works
- Authors
- Govek, K. W., Chen, S., Sgourdou, P., Yao, Y., Woodhouse, S., Chen, T., Fuccillo, M. V., Epstein, D. J., & Camara, P. G.
- Affiliations
- University of Pennsylvania (US)
- University of Georgia (US)
- Corresponding author
- Epstein, Douglas J.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 41
- Issue
- 10
- Pages
- 111768
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC9880597
- OpenAlex
- W4310858776
- Cited by
- 28
- References
- 73
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 7 · 2023: 2
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Funders
- National Institute of Neurological Disorders and Stroke (R01 NS039421)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- thalamus development, Sonic hedgehog, intermediate progenitor cells, thalamic nuclei, neural lineage specification, transcriptional programs, locomotor impairment, neurodevelopmental disorders, embryonic brain development
- MeSH terms
- Thalamus
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