MULTIPLE ESSENTIAL FUNCTIONS OF NEUREGULIN IN DEVELOPMENT
MULTIPLE ESSENTIAL FUNCTIONS OF NEUREGULIN IN DEVELOPMENT
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DOI：
10.1038/378386a0
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发表时间：
1995-11-23
期刊：
影响因子：
64.8
通讯作者：
BIRCHMEIER, C
中科院分区：
文献类型：
--
作者：
MEYER, D;BIRCHMEIER, C
神经调节蛋白（也称为NDF、heregulin、GGF和ARIA）是EGF家族的成员，其诱导培养物中上皮细胞、神经胶质细胞和肌肉细胞的生长和分化（1-4）。该因子的生物学效应由酪氨酸激酶受体介导。神经调节蛋白可以直接与erbB 3和erbB 4结合，受体异源二聚化允许神经调节蛋白依赖性激活erbB 2（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中的多种重要作用。此外，雪旺氏细胞前体和颅神经节不能正常发育。表型表明，在体内neuregulin的行为，局部和频繁的旁分泌方式。受突变影响的所有细胞类型表达erbB 3或erbB 4，表明这些酪氨酸激酶受体中的任一种都可以是识别和传递必需的神经调节蛋白信号的组分。
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(1-4). 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.