Investigating fibins in zebrafish development and regeneration
File(s)
Author(s)
Rydlova, Anna
Type
Thesis
Abstract
Zebrafish, Danio rerio, is a widely accepted model of tissue regeneration. Yet, thorough
understanding of the cellular and molecular pathways that govern the tightly regulated
responses to injury still remain to be fully understood. Characterization of these molecular
events holds a great potential for translational application in number of human disorders,
including chronic fibrotic diseases. Transcript levels of the vertebrate-specific gene Fibin
were found to be significantly increased in a zebrafish model of gill tissue regeneration
compared to mouse models of pulmonary fibrosis, suggesting a potential role of Fibins in
scar-less tissue regeneration. In this thesis, I used zebrafish as a model organism to
investigate Fibins in development, and in adult tissue regeneration.
Using RNA-seq analysis, flow cytometry and RNA analysis techniques I characterised the
immune cell composition in the gills and WKM as well as the immune responses to viral
mimetic compound, R848, in the wild-type and double-mutant (fibina/b-/-) zebrafish. Using
several microscopy techniques, I have investigated the impact of lack of functional Fibins on
the development of craniofacial cartilage and bone. I investigated the regenerative capacities
and differential molecular signatures of regenerating gill and caudal fin tissues between the
wild-type and fibina/b-/- adult fish. And finally, using in vitro assays, I have investigated the
molecular pathways that regulate FIBIN expression in human primary pulmonary fibroblasts.
The RNA-seq analysis highlighted number of differentially expressed genes between the
wild-type and fibina/b-/- fish. These genes were enriched for immune function and BMP
signalling pathway components, in particular BMP-signalling antagonists. Characterization of
the haematopoietic cells as well as of the ability to mount an immune response to R848 did
not show significant differences between the wild type and fibina/b-/- fish...
understanding of the cellular and molecular pathways that govern the tightly regulated
responses to injury still remain to be fully understood. Characterization of these molecular
events holds a great potential for translational application in number of human disorders,
including chronic fibrotic diseases. Transcript levels of the vertebrate-specific gene Fibin
were found to be significantly increased in a zebrafish model of gill tissue regeneration
compared to mouse models of pulmonary fibrosis, suggesting a potential role of Fibins in
scar-less tissue regeneration. In this thesis, I used zebrafish as a model organism to
investigate Fibins in development, and in adult tissue regeneration.
Using RNA-seq analysis, flow cytometry and RNA analysis techniques I characterised the
immune cell composition in the gills and WKM as well as the immune responses to viral
mimetic compound, R848, in the wild-type and double-mutant (fibina/b-/-) zebrafish. Using
several microscopy techniques, I have investigated the impact of lack of functional Fibins on
the development of craniofacial cartilage and bone. I investigated the regenerative capacities
and differential molecular signatures of regenerating gill and caudal fin tissues between the
wild-type and fibina/b-/- adult fish. And finally, using in vitro assays, I have investigated the
molecular pathways that regulate FIBIN expression in human primary pulmonary fibroblasts.
The RNA-seq analysis highlighted number of differentially expressed genes between the
wild-type and fibina/b-/- fish. These genes were enriched for immune function and BMP
signalling pathway components, in particular BMP-signalling antagonists. Characterization of
the haematopoietic cells as well as of the ability to mount an immune response to R848 did
not show significant differences between the wild type and fibina/b-/- fish...
Version
Open Access
Date Issued
2023-07-23
Date Awarded
01/11/2023
License URL
Advisor
Dallman, Maggie
Sponsor
Böhringer Ingelheim (Firm)
Biotechnology and Biological Sciences Research Council (Great Britain)
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)