Project information
Low stability of FGF morphogens in regulation of early mammalian limb development
(Regulace časného vývoje savčí končetiny)
- Project Identification
- GA19-20123S
- Project Period
- 1/2019 - 12/2021
- Investor / Pogramme / Project type
-
Czech Science Foundation
- Standard Projects
- MU Faculty or unit
- Faculty of Medicine
Fibroblast growth factors (FGFs) are among the key regulators of organ morphogenesis, but many of the mechanisms underlying FGF function during development remain unclear. FGFs are inherently unstable proteins, and their biological activity in vitro is significantly limited by this instability. According to our hypothesis, the low stability of key morphogens from the FGF family, such as FGF8 and FGF10, has evolved as a mechanism to prevent uncontrolled FGF signalling during morphogenesis. In the proposed project, we will test this hypothesis by determining the effect of FGF stabilisation on the early development of the mammalian limb. Using rationally designed mutagenesis, we will experimentally stabilise the FGF8 and FGF10 proteins by increasing their resistance to thermal denaturation and proteolytic degradation. The stabilising mutations will then be introduced into mouse Fgf8 and Fgf10 in vivo via genetic manipulation, thereby creating animal models expressing stable Fgf8 and Fgf10. In these models, we will subsequently determine the effect of FGF8 and FGF10 stabilisation on limb development.
Publications
Total number of publications: 8
2024
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Ligand bias underlies differential signaling of multiple FGFs via FGFR1
elife, year: 2024, volume: 12, edition: April 2024, DOI
2022
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4-PBA Treatment Improves Bone Phenotypes in the Aga2 Mouse Model of Osteogenesis Imperfecta
Journal of bone and mineral research, year: 2022, volume: 37, edition: 4, DOI
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Expanding horizons of achondroplasia treatment: current options and future developments
Osteoarthritis and Cartilage, year: 2022, volume: 30, edition: 4, DOI
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LuminoCell: a versatile and affordable platform for real-time monitoring of luciferase-based reporters
Life science alliance, year: 2022, volume: 5, edition: 8, DOI
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Lyn Phosphorylates and Controls ROR1 Surface Dynamics During Chemotaxis of CLL Cells
Frontiers in Cell and Developmental Biology, year: 2022, volume: 10, edition: February 2022, DOI
2021
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An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice
Science Translational Medicine, year: 2021, volume: 13, edition: 592, DOI
2020
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Biallelic mutations in LAMA5 disrupts a skeletal noncanonical focal adhesion pathway and produces a distinct bent bone dysplasia
EBioMedicine, year: 2020, volume: 62, edition: DEC 2020, DOI
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Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling
EMBO MOLECULAR MEDICINE, year: 2020, volume: 12, edition: 11, DOI