SCHLUETER, P.J.*; DUAN, C.; University of Michigan, Ann Arbor; University of Michigan, Ann Arbor: Overlapping and distinct functions of the duplicated zebrafish insulin-like growth factor-1 receptor (IGF-1R) genes in early development

The process of gene duplication is a major contributor to the genetic diversity of vertebrate genomes, and the driving force behind a complicated process of functional gene evolution, involving both the acquisition of new functions and the rearrangement of ancestral functions. Deciphering whether a pair of duplicated genes have acquired new functions, or subdivided their ancestral functions, is an important but challenging question. Among vertebrates, the zebrafish is well suited for investigations into this question because of its versatility, and because it possess a large number of duplicated genes. Previous studies have shown that there are two structurally distinct and functional insulin-like growth factor 1 receptor (igf1r) genes in zebrafish, in contrast to the presence of a single IGF1R gene in mammals. IGF1R-mediated signaling is an evolutionarily ancient signaling pathway that plays fundamental roles in regulating growth, development, metabolism, and longevity. In this study, we tested the hypothesis that gene duplication has led to the functional divergence of zebrafish igf1ra and igf1rb in development using a MO-based loss-of-function approach. Our results indicated that igf1ra and igf1rb are not redundant genes, as both are essential for zebrafish viability and somatic growth and development. Although Igf1ra and Igf1rb demonstrated a large degree of functional overlap with regard to cell differentiation and survival in the eye, inner ear, and heart, they also demonstrated functional distinction involving a greater requirement for Igf1rb in spontaneous muscle contractility and motoneuron axon formation. These findings provide novel insights into the functional evolution of the IGF1R/insulin receptor gene family.