Haploinsufficient maternal effect of Epidermal Growth Factor Receptor A mutation in zebrafish

Abstract

AbstractGeneration of viable offspring depends both on genetic and environmental factors of both mother and child. Analysis of a likely amorphic allele of the zebrafish epidermal growth factor receptor a (egfra) gene revealed that heterozygous females were infertile due to death of all fertilized eggs during embryonic and early larval life with cardiac, tail and other defects. Comparison of the severe dominant maternal effect with previous studies using pharmacological inhibitors of Egfrs or antisense morpholino injection indicate that a normal level of maternal Egfra is required for viability of offspring both during egg development and in the embryo after fertilisation. As heterozygous mothers were not fertile, the homozygous zygotic egfrakg134 phenotype could not be analysed. Heterozygous egfra+/kg134 males crossed to wild type females produced fully viable offspring, among which egfra+/kg134 individuals had increased slow muscle but no functional motility defect. Our findings suggest that Egfra activity is crucial for early development both before and after fertilisation and are likely to constitute a rare example of a haploinsufficient maternal effect in a species lacking imprinting.