ArticleScience advances2020
A Shh/Gli-driven three-node timer motif controls temporal identity and fate of neural stem cells.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids.Nature communications · 2026Article
- Gli2 and Gli3 synergistically mediate HH-TGF-β crosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesis.International journal of oral science · 2026Article
- O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery.Nature communications · 2022Article
- Precision of morphogen gradients in neural tube development.Nature communications · 2022Article
- A shared transcriptional code orchestrates temporal patterning of the central nervous system.PLoS biology · 2021Article
- Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.PLoS computational biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How time is measured by neural stem cells during temporal neurogenesis has remained unresolved. By combining experiments and computational modeling, we define a Shh/Gli-driven three-node timer underlying the sequential generation of motor neurons (MNs) and serotonergic neurons in the brainstem. The timer is founded on temporal decline of Gli-activator and Gli-repressor activities established through down-regulation of Gli transcription. The circuitry conforms an incoherent feed-forward loop, whereby Gli proteins not only promote expression of Phox2b and thereby MN-fate but also account for a delayed activation of a self-promoting transforming growth factor-β (Tgfβ) node triggering a fate switch by repressing Phox2b. Hysteresis and spatial averaging by diffusion of Tgfβ counteract noise and increase temporal accuracy at the population level, providing a functional rationale for the intrinsically programmed activation of extrinsic switch signals in temporal patterning. Our study defines how time is reliably encoded during the sequential specification of neurons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.