AGING ZEBRAFISH CIRCULI PDF

Skeletal structures have a collagen-rich matrix that provides shape, organ protection, endocrine, and locomotive functions to the organism. The vertebrate skeleton is composed of non-mineralised cartilage and mineralised bone, enamel, and dentine structures.

Zebrafish mutants of two human orthologues that were robustly associated with height ( COL11A2, P=6× 10 −24) or eBMD ( SPP1, P=6× 10 −20) showed both exo- and endo- skeletal abnormalities as predicted by our genetic association analyses col11a2 Y228X/Y228X mutants showed exoskeletal and endoskeletal features consistent with abnormal growth, whereas spp1 P160X/P160X mutants predominantly showed mineralisation defects. The DEGs were also enriched for human orthologues associated with polygenetic skeletal traits, including height ( P< 6× 10 −4), and estimated bone mineral density (eBMD, P< 2× 10 −5). Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases ( P< 2× 10 −3). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). Scatterplots describing pairwise comparisons of ancestry informative PCA components. Scatterplots describing pairwise comparisons of ancestry informative UMAP components Figure S11. Histomorphological measurements of skeletal elements from wildtype Figure S10. Von Kossa staining of spp1 and col11a2 mutant ontogenetic and regenerating scales Figure S9. MAGMA competitive gene set analysis involving human polygenetic traits and disease Figure S8. Quantitative Real-Time PCR analysis of RNA expression of bone markers Figure S7. STRING Network analysis showing high protein-protein interaction connectivity of DEGs Figure S6. Hierarchical clustering of ‘Biological Process’ enriched gene ontology terms Figure S5. Hierarchical clustering of ‘Molecular Function’ enriched gene ontology terms using GOrilla web interface Figure S4. Two top down regulated genes are on the same genomic contig but are not the same protein Figure S3. Ontogenetic and regenerating differential expression values are clustered together Figure S2. DEGs identified belonging to isolated clusters (1-4) with no identified gene ontology Figure S1.

AGING ZEBRAFISH CIRCULI PDF

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Aging zebrafish circuli