PUBLICATION
Nodal signaling establishes a competency window for stochastic cell fate switching
- Authors
- Economou, A.D., Guglielmi, L., East, P., Hill, C.S.
- ID
- ZDB-PUB-221207-4
- Date
- 2022
- Source
- Developmental Cell 57: 26042622.e52604-2622.e5 (Journal)
- Registered Authors
- Hill, Caroline
- Keywords
- FGF, Nodal, endoderm specification, mesoderm specification, morphogen gradient, stochastic cell switching
- MeSH Terms
-
- Animals
- Zebrafish*
- PubMed
- 36473458 Full text @ Dev. Cell
Citation
Economou, A.D., Guglielmi, L., East, P., Hill, C.S. (2022) Nodal signaling establishes a competency window for stochastic cell fate switching. Developmental Cell. 57:26042622.e52604-2622.e5.
Abstract
Specification of the germ layers by Nodal signaling has long been regarded as an archetype of how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset of cells at the early zebrafish embryo margin adopt the endodermal fate, whereas their immediate neighbours, experiencing a similar signaling environment, become mesoderm. Combining pharmacology, quantitative imaging and single cell transcriptomics, we demonstrate that sustained Nodal signaling establishes a bipotential progenitor state from which cells can switch to an endodermal fate or differentiate into mesoderm. Switching is a random event, the likelihood of which is modulated by Fgf signaling. This inherently imprecise mechanism nevertheless leads to robust endoderm formation because of buffering at later stages. Thus, in contrast to previous deterministic models of morphogen action, Nodal signaling establishes a temporal window when cells are competent to undergo a stochastic cell fate switch, rather than determining fate itself.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping