Tgfβ signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS
Open accessAbstract
How the sequential specification of neurons and progressive loss of potency associated with aging neural progenitors are regulated in vertebrate brain development is poorly understood. By examining a temporal differentiation lineage in the hindbrain, we here identify Tgfβ as a switch signal that executes the transition between early and late phases of neurogenesis and concurrently constrains progenitor potency. Young progenitors have inherent competence to produce late-born neurons, but implementation of late-differentiation programs requires suppression of early identity genes achieved through temporally programmed activation of Tgfβ downstream of Shh signaling. Unexpectedly, we find that sequentially occurring fate-switch decisions are temporally coupled, and onset of Tgfβ signaling appears thereby to impact on the overall lifespan of the temporal lineage. Our study establishes Tgfβ as a regulator of temporal identity and potency of neural stem cells, and provides proof of concept that Tgfβ can be applied to modulate temporal specification of neurons in stem cell engineering.
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TGFβ signalling has been shown to suppress early born neuronal identities in favour of later born cell types in multiple regions of the nervous system.
“Another candidate for mediating the temporal progression of neuronal subtypes is TGFβ signalling, which has been shown to suppress early born neuronal identities in favour of later born cell types in multiple regions of the nervous system (Dias et al., 2014).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Dias et al., 2014
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- Authors
- Dias, J. M., Alekseenko, Z., Applequist, J. M., & Ericson, J.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Ericson, Johan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 84
- Issue
- 5
- Pages
- 927-939
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2049880398
- Cited by
- 99
- References
- 43
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 10 · 2014: 1
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse
- 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 › Congenital heart defects research
- Keywords
- TGF-beta signaling, Sonic hedgehog signaling, hindbrain development, neuronal fate specification, lineage specification, stem cell engineering, brain development
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Homeobox Protein Nkx-2.2, Age Factors, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Central Nervous System, Chick Embryo, Embryo, Mammalian, Female, Mice, Transgenic, Organ Culture Techniques, Pregnancy, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Homeodomain Proteins, Gene Expression Regulation, Developmental, Zebrafish Proteins, Mice, Neural Tube, Neurogenesis, Neural Stem Cells
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