ZFIN ID: ZDB-PUB-180909-4
Cre/lox-controlled spatio-temporal perturbation of FGF signaling in zebrafish
Kirchgeorg, L., Felker, A., van Oostrom, M., Chiavacci, E., Mosimann, C.
Date: 2018
Source: Developmental dynamics : an official publication of the American Association of Anatomists   247(10): 1146-1159 (Journal)
Registered Authors: Chiavacci, Elena, Felker, Anastasia, Mosimann, Christian
Keywords: Cre/lox, FGF, heatshock, transgenes, zebrafish, signaling
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Fibroblast Growth Factors/metabolism*
  • Integrases/metabolism
  • Mesoderm/metabolism
  • Signal Transduction*
  • Spatio-Temporal Analysis*
  • Zebrafish/embryology
  • Zebrafish/metabolism*
PubMed: 30194800 Full text @ Dev. Dyn.
Spatio-temporal perturbation of signaling pathways in vivo remains challenging and requires precise transgenic control of signaling effectors. Fibroblast Growth Factor (FGF) signaling guides multiple developmental processes including body axis formation and cell fate patterning. In zebrafish, mutants and chemical perturbations affecting FGF signaling have uncovered key developmental processes; however, these approaches cause embryo-wide perturbations, rendering assessment of cell-autonomous versus non-autonomous requirements for FGF signaling in individual processes difficult.
Here, we created the novel transgenic line fgfr1-dn-cargo, encoding dominant-negative Fgfr1 with fluorescent tag under combined Cre/lox and heatshock control to perturb FGF signaling spatio-temporally. Validating efficient perturbation of FGF signaling by fgfr1-dn-cargo primed with ubiquitous CreERT2, we established that primed, heatshock-induced fgfr1-dn-cargo behaves akin to pulsed treatment with the FGFR inhibitor SU5402. Priming fgfr1-dn-cargo with CreERT2 in the lateral plate mesoderm triggered selective cardiac and pectoral fin phenotypes without drastic impact on overall embryo patterning. Harnessing lateral plate mesoderm-specific FGF inhibition, we recapitulated the cell-autonomous and temporal requirement for FGF signaling in pectoral fin outgrowth, as previously inferred from pan-embryonic FGF inhibition.
As paradigm for rapid Cre/lox-mediated signaling perturbations, our results establish fgfr1-dn-cargo as a genetic tool to define the spatio-temporal requirements for FGF signaling in zebrafish. This article is protected by copyright. All rights reserved.