ISOFORM-SPECIFIC EXPRESSION AND FUNCTION OF NEUREGULIN

Neuregulin (also known as NDF, heregulin, ARIA, GGF or SMDF), induces cell growth and differentiation. Biological effects of neuregulin are mediated by members of the erbB family of tyrosine kinase receptors. T hree major neuregulin isoforms are produced from the gene, which diffe r substantially in sequence and in overall structure, Here we use in s itu hybridization with isoform-specific probes to illustrate the spati ally distinct patterns of expression of the isoforms during mouse deve lopment. Ablation of the neuregulin gene in the mouse has demonstrated multiple and independent functions of this factor in development of b oth the nervous system and the heart. We show here that targeted mutat ions that affect different isoforms result in distinct phenotypes, dem onstrating that isoforms can take over specific functions in vivo, Typ e I neuregulin is required for generation of neural crest-derived neur ons in cranial ganglia and for trabeculation of the heart ventricle, w hereas type III neuregulin plays an important role in the early develo pment of Schwann cells, The complexity of neuregulin functions in deve lopment is therefore due to independent roles played by distinct isofo rms.