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
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.
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