Cited by 99Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital heart defects research

Tgfβ signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS

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Dias, José M., Alekseenko, Zhanna, Applequist, Joanna M., Ericson, Johan·2014·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2014.10.033

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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).”

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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
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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