Zebra balığının model organizma olarak kullanılarak melanosit rejenerasyonu ve melanomun moleküler mekanizmalarının karşılaştırılması

Molecular mechanisms underlying regeneration and cancer have always been a challenging question. Studies that seek an answer to the common/different behaviors of these distinct processes are rare. Early regeneration involves rapid but controlled proliferation of progenitor cells. However, the clear distinction between regeneration and cancerization appears to happen as regenerating cell population decelerate proliferation, lose migratory features, mesenchymal characteristic and acquire differentiation, in a way unlike cancer cell population. Therefore, we hypothesized that molecular mechanism shared by cancerization and regeneration is similar at early stages whereas the cellular mechanisms must become dissimilar at the later stages. We used adult zebrafish as a model to test our hypothesis because it has high pigment regeneration capacity and rapid melanoma growth upon transgenic approaches. Besides, many tumor suppressors and oncogenes are conserved between zebrafish and human. We established melanocyte regeneration and melanoma models of zebrafish on caudal fin. We ablated melanocytes in adult zebrafish by Neocuproine (NCP) and determined early and late stages of melanocyte regeneration as one dpa and seven dpa, respectively. We used mitfa-/- (nacre); kita:GFP-RASG12V line to generate melanoma models. Within two months, both hyper-pigmented and hypo-pigmented melanoma arose in crossbreeds of mitfa-/- (nacre); kita:GFP-RASG12V and wild type (AB). We checked the expression levels of early and late melanocyte regeneration markers and neural crest cell markers for zebrafish melanoma. We found out that differentiation markers were high in hyper-pigmented melanoma while neural crest cell markers were high in hypo-pigmented melanoma. All in all, these observations may provide ground for the studies that would investigate melanocyte regeneration and melanoma on zebrafish model. Keywords: Melanocyte, Melanoma, Regeneration, Zebrafish, Early and Later Stages