The role of Gdf5 in the development of the zebrafish fin endoskeleton

Abstract

AbstractBackgroundThe development of the vertebrate limb skeleton requires a complex interaction of multiple factors to facilitate correct shaping and positioning of bones and joints. Growth and differentiation factor 5 (Gdf5), a member of the transforming growth factor-beta family (TGF-β) is involved in patterning appendicular skeletal elements including joints. Expression of gdf5 in zebrafish has been detected within the first pharyngeal arch jaw joint, fin mesenchyme condensations and segmentation zones in median fins, however little is known about the functional role of Gdf5 outside of Amniota.ResultsWe generated CRISPR/Cas9 knockout of gdf5 in zebrafish and analysed the resulting phenotype at different developmental stages. Homozygous gdf5 mutant zebrafish displayed changes in segmentation of the endoskeletal disc and, in consequence, loss of posterior radials in the pectoral fins. Mutant fish also displayed affected organisation and length of skeletal elements in the median fins, however joint formation and mineralisation process seemed unaffected.ConclusionsOur study demonstrates the importance of Gdf5 for the paired and median fin endoskeleton development in zebrafish and reveals that the severity of the effect increases from anterior to posterior side of the elements. Our findings are consistent with phenotypes observed in human and mouse appendicular skeleton in response to Gdf5 knockout, suggesting a broadly conserved role for Gdf5 in Osteichthyes.