Grant: CIHR Fellowship

Fibroblasts provide structural support to our body by producing the extracellular matrix, a scaffold-like material. Beyond this role, they also play important roles in wound healing, inflammation, cancer, and tissue scarring. While fibroblasts were once thought to be a single cell type, recent studies have revealed a wide variety of fibroblast subtypes, found both across different organs and even within the same tissue. Our research focuses on understanding how these diverse fibroblast subtypes are generated during embryonic development, using zebrafish as a model. Zebrafish share 70% genetic similarity with humans, and key cell signaling pathways involved in organ development are highly conserved, making them an ideal model for studying fibroblast development. My research demonstrates that disrupting the platelet-derived growth factor (PDGF) signaling pathway, a conserved cell-to-cell communication pathway, completely abolishes the migration and subsequent differentiation of multiple fibroblast populations. Interestingly, I found that specific ligands for the PDGF pathway are expressed in localized regions during development, and the loss of one ligand affects only certain fibroblast populations, while others develop normally. I will determine how different PDGF ligands function to guide fibroblasts to specific regions of the embryo. Additionally, I will investigate whether fibroblasts are guided by similar mechanisms during tissue injury repair in a tendon regeneration model. The findings of this study will inform new therapeutic strategies to manipulate fibroblasts to promote tissue repair and regeneration.