Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation.
Diffusion
Fgf8a
Morphogen
Neural plate
Patterning
Zebrafish
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
received:
04
01
2023
accepted:
29
08
2023
medline:
4
10
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
ppublish
Résumé
Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.
Identifiants
pubmed: 37665167
pii: 330697
doi: 10.1242/dev.201559
pmc: PMC10565248
pii:
doi:
Substances chimiques
Zebrafish Proteins
0
fgf8a protein, zebrafish
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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