ABSTRACT
Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the function of fibroblasts has been extensively studied in adults, the embryonic origin and diversification of different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that the sclerotome, a sub-compartment of the somite, is the embryonic source of multiple fibroblast populations, including tenocytes (tendon fibroblasts), blood vessel associated fibroblasts, and fin mesenchymal cells. High resolution imaging shows that different fibroblast subtypes occupy unique anatomical locations with distinct morphologies. Photoconversion-based cell lineage analysis reveals that sclerotome progenitors at different dorsal-ventral and anterior-posterior positions display distinct differentiation potentials. Single cell clonal analysis suggests that sclerotome progenitors are multipotent, and the fate of their daughter cells is biased by their migration paths and relative positions. Using a small molecule inhibitor, we show that BMP signaling is required for the development of fin mesenchymal cells in the peripheral fin fold. Together, our work demonstrates that the sclerotome contains multipotent progenitors that respond to local signals to generate a diverse population of tissue-resident fibroblasts.
AUTHOR SUMMARY Fibroblasts are present in most organs in our body. They not only provide structural support to corresponding tissues, but also play important roles in wound healing and tissue fibrosis. Although the function of fibroblasts has been well appreciated, how different tissue-resident fibroblasts emerge during embryonic development is still poorly understood. Using the zebrafish model, we identify the sclerotome, a sub-compartment of the embryonic somite, as the main source of multiple fibroblast populations. Different fibroblast subtypes display distinct morphologies and locate at unique positions to support different tissues, including the muscles, blood vessels and the fin fold. Using cell tracing in live animals, we find that single sclerotome progenitors are able to generate more than one type of fibroblasts. The differentiation potential of sclerotome progenitors is biased by their initial locations in the trunk as well as their migration directions and relative positions. Local BMP signaling in the fin fold is essential for the proper development of sclerotome derived fin mesenchymal cells. Together, our results show that local microenvironment contributes to the diversification of multipotent sclerotome progenitors into distinct fibroblast subtypes.
