Caracterização dos mecanismos envolvidos no desenvolvimento e pigmentação da pelagem de mamíferos utilizando redes de interações moleculares

Abstract

Although the genetic bases of mammalian pigmentation have been extensively studied, the complex interactions among the pathways and genes that affect this trait have not been fully characterized. Furthermore, the molecular bases of periodic coat patterning, such as stripes and spots, an important phenotype in several aspects of species biology, are still incompletely understood. These questions can be explored with systems biology approaches, by assessing known and predicting new interactions among proteins along with using network properties to characterize them. By exploring a given trait as a system, instead of isolated genes, we can better understand and characterize complex phenotypes such as the mammalian coat. Here, we applied this strategy to mammalian pelage features and constructed an interaction network using a dataset of mouse pigmentation and hair growth genes. In addition, we also specifically searched for genes interacting with two loci (Lvrn and Alx3) that are known to participate in the mechanism of coat periodic patterning in cats and rodents, respectively, and merged their networks with the main coat-related network. On these networks, we performed centrality analyses and explored their connections. Our results indicated that genes belonging to the Wnt pathway play particularly important roles in these phenotypes, along with endothelin signaling, immunity, cell adhesion, angiogenesis, growth factors, apoptosis and cell survival, and proopiomelanocortin. This result illustrates the complex interplay among the diversity of pathways that affect the mammalian coat. With regard to periodic patterning, we observed that Alx3 and Lvrn connect to pigmentation pathways at distinct positions, supporting the inference that they act via distinct mechanisms. Furthermore, we identified genes playing a role in pelage phenotypes, such as Ets1 and Sfn, that potentially connect mammalian pigmentation pathways with those related to Lvrn-based patterning, thus providing novel candidates for experimental assessments of this intriguing phenotype.