ERBB3 IS REQUIRED FOR NORMAL CEREBELLAR AND CARDIAC DEVELOPMENT - A COMPARISON WITH ERBB2-DEFICIENT AND HEREGULIN-DEFICIENT MICE

Heregulins bind directly to ErbB3 and ErbB4 receptors, leading to mult iple dimerization possibilities including heterodimerization with the ErbB2 receptor, We have generated ErbB3-, ErbB2- and heregulin-deficie nt mice to assess their roles in development and differentiation. Here gulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a lack of cardi ac ventricular myocyte differentiation; ErbB3(-/-) embryos survived un til E13.5 exhibiting cardiac cushion abnormalities leading to blood re flux through defective valves. In ErbB3(-/-) embryos, the midbrain/hin dbrain region was strikingly affected, with little differentiation of the cerebellar plate. Cranial ganglia defects, while present in all th ree nulls, were less severe in ErbB3(-/-) embryos. The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ga nglia and adrenal chromaffin cells, suggests a generalized effect on t he neural crest. Numerous organs, including the stomach and pancreas a lso exhibited anomalous development.