Unique and Non-redundant Function of Paralogues in Regulation and Evolution of Post-embryonic Development of the Zebrafish

Evolution is replete with reuse of genes in different contexts, leading to multifunctional roles of signaling factors during development. Here, we explore osteoclast regulation during skeletal development through analysis of colony-stimulating factor 1 receptor () function in the zebrafish. A primary role of Csf1r signaling is to regulate the proliferation, differentiation and function of myelomonocytic cells, including osteoclasts. We demonstrate the retention of two functional paralogues of in zebrafish. Mutant analysis indicates that the paralogues have shared, non-redundant roles in regulating osteoclast activity during the formation of the adult skeleton. , however, has adopted unique roles in pigment cell patterning not seen in the second paralogue. We identify a unique noncoding element within of fishes that is sufficient for controlling gene expression in pigment cells during development. As a role for Csf1r signaling in pigmentation is not observed in mammals or birds, it is likely that the overlapping roles of the two paralogues released functional constraints on , allowing the signaling capacity of Csf1r to serve a novel function in the evolution of pigment pattern in fishes.