Meyer D, Birchmeier C
Nature. 1995 Nov 23;378(6555):386-90. doi: 10.1038/378386a0.
Neuregulin (also called NDF, heregulin, GGF and ARIA) is a member of the EGF family which induces growth and differentiation of epithelial, glial and muscle cells in culture. The biological effects of the factor are mediated by tyrosine kinase receptors. Neuregulin can bind directly to erbB3 and erbB4 and receptor heterodimerization allows neuregulin-dependent activation of erbB2 (refs 1, 2, 5). A targeted mutation in mice reveals multiple essential roles of neuregulin in development. Here we show that neuregulin -/- embryos die during embryogenesis and display heart malformations. In addition, Schwann cell precursors and cranial ganglia fail to develop normally. The phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner. All cell types affected by the mutation express either erbB3 or erbB4, indicating that either of these tyrosine kinase receptors can be a component in recognition and transmission of essential neuregulin signals.
神经调节蛋白（也称为NDF、这里调节蛋白、GGF和ARIA）是表皮生长因子（EGF）家族的成员，在培养中可诱导上皮细胞、神经胶质细胞和肌肉细胞的生长与分化。该因子的生物学效应由酪氨酸激酶受体介导。神经调节蛋白可直接与erbB3和erbB4结合，受体异二聚化可使神经调节蛋白依赖的erbB2激活（参考文献1、2、5）。小鼠中的靶向突变揭示了神经调节蛋白在发育过程中的多种重要作用。在此我们表明，神经调节蛋白基因敲除（-/-）胚胎在胚胎发生过程中死亡，并表现出心脏畸形。此外，雪旺细胞前体和颅神经节无法正常发育。该表型表明，在体内神经调节蛋白通常以旁分泌方式局部发挥作用。受该突变影响的所有细胞类型均表达erbB3或erbB4，这表明这两种酪氨酸激酶受体中的任何一种都可能是识别和传递重要神经调节蛋白信号的组成部分。
