Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
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 (FCS), we demonstrate that Fgf8a, 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 critical for it to achieve its morphogenic potential.
Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | dev201559 |
| Fachzeitschrift | Development (Cambridge, England) |
| Jahrgang | 150 |
| Ausgabenummer | 19 |
| Publikationsstatus | Veröffentlicht - 4 Sept. 2023 |
| Peer-Review-Status | Ja |
Externe IDs
| unpaywall | 10.1242/dev.201559 |
|---|---|
| ORCID | /0000-0002-7133-7474/work/142251282 |
| ORCID | /0000-0003-0283-0211/work/142257357 |
| Scopus | 85174319944 |
Schlagworte
Forschungsprofillinien der TU Dresden
- Gesundheitswissenschaften, Biomedizin und Bioengineering - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Biophysik und Bioengineering - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Regenerative Therapien - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Neurowissenschaften - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Metabolische Erkrankungen - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
DFG-Fachsystematik nach Fachkollegium
- Molekulare Biologie und Physiologie von Nerven- und Gliazellen - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Entwicklungsneurobiologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Biomaterialien - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Entwicklungsbiologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Allgemeine Genetik und funktionelle Genomforschung - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Molekulare und zelluläre Neurologie und Neuropathologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Immunologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Zellbiologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Biophysik - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Biochemie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
Ziele für nachhaltige Entwicklung
- SDG 3 – Gute Gesundheit und Wohlergehen - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
ASJC Scopus Sachgebiete
- Molekularbiologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- Entwicklungsbiologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
Schlagwörter
- Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
Bibliotheksschlagworte
- 570 Biowissenschaften; Biologie - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics
- 610 Medizin und Gesundheit - Animals, Body Patterning/genetics, Fibroblast Growth Factors/genetics, Gastrulation/genetics, Morphogenesis/genetics, Signal Transduction/genetics, Zebrafish, Zebrafish Proteins/genetics