Maternal Larp6 controls oocyte development, chorion formation and elevation

Abstract

La-related protein 6 (Larp6) is a conserved RNA-binding protein found across eukaryotes that has been suggested to regulate collagen biogenesis, muscle development, ciliogenesis, and various aspects of cell proliferation and migration. Zebrafish have two Larp6 family genes: <i>larp6a</i> and <i>larp6b</i> Viable and fertile single and double homozygous <i>larp6a</i> and <i>larp6b</i> zygotic mutants revealed no defects in muscle structure, and were indistinguishable from heterozygous or wild-type siblings. However, <i>larp6a</i> mutant females produced eggs with chorions that failed to elevate fully and were fragile. Eggs from <i>larp6b</i> single mutant females showed minor chorion defects, but chorions from eggs laid by <i>larp6a;larp6b</i> double mutant females were more defective than those from <i>larp6a</i> single mutants. Electron microscopy revealed defective chorionogenesis during oocyte development. Despite this, maternal zygotic single and double mutants were viable and fertile. Mass spectrometry analysis provided a description of chorion protein composition and revealed significant reductions in a subset of zona pellucida and lectin-type proteins between wild-type and mutant chorions that paralleled the severity of the phenotype. We conclude that Larp6 proteins are required for normal oocyte development, chorion formation and egg activation.