Babcock, Ǵerald

Members of the epidermal growth factor family and its receptors (EGFR/ErbBs 1–4) critically regulate the development and maintenance of numerous tissues including CNS, heart, kidney, GI tract, and muscle, accounting for a variety of congenital malformations, tumor growth, renal cyst formation, and heart failure. We cloned erbB4 from zebrafish (Danio rerio) and examined its effects on embryonic development by reducing its expression through injection of antisense morpholinos (MO) into zebrafish embryos at the 1–2 cell‐stage. Zebrafish ErbB4 was 73% identical to rat and human ErbB4. In situ hybridization using two non‐overlapping probes both showed expression 10 hours post‐fertilization throughout the embryo with expression resolving to the brain, eye, heart, kidney, and GI tract (intestine, liver, pancreas) over the next 5 days. Injection of two 5′ non‐overlapping MO both demonstrated altered development of multiple organs including brain, eyes, heart, and tail. Effects ranged in severity from complete lack of head, heart, and tail formation to stunted head, eye, and tail formation, distended pericardium, and unfolded heart tube. These studies demonstrate multiple critical roles for ErbB4 in development, and the utility of the zebrafish model system for these studies. AHA30137N, EY017732 , Case Aces/NSF Advance, Wadsworth Foundation.