Meyer D, Birchmeier C
Max-Delbrück-Laboratorium in der Max-Planck-Gesellschaft, Koeln, Germany.
Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1064-8. doi: 10.1073/pnas.91.3.1064.
Neuregulin, the putative ligand of the c-neu receptor tyrosine kinase, can induce differentiation or growth of epithelia and other cells. To gain insight into the biological role of this factor, we have analyzed the expression of neuregulin during mouse embryogenesis and in the perinatal animal by a combination of in situ hybridization and RNase protection experiments. We identify sites of expression that correspond to mesenchymal cells of various parenchymal organs. Our finding implies a function of neuregulin as a mesenchymal factor that acts on epithelia. The mesenchymal expression of neuregulin could thus provide a molecular basis for the biological phenomenon of mesenchymal-epithelial interactions. It also has implications on the molecular mechanism by which amplification of c-neu can affect tumor progression of carcinomas. In addition, neuregulin expression is found in neuronal cells during development. We show by RNase protection experiments that distinct isoforms of neuregulin are expressed in the brain. Therefore, our data indicate in vivo a dual role for neuregulin as mesenchymal and neuronal factor.
神经调节蛋白是原癌基因c-neu受体酪氨酸激酶的假定配体，可诱导上皮细胞和其他细胞的分化或生长。为深入了解该因子的生物学作用，我们通过原位杂交和核糖核酸酶保护实验相结合的方法，分析了神经调节蛋白在小鼠胚胎发育过程以及围产期动物中的表达情况。我们确定了与各种实质器官的间充质细胞相对应的表达位点。我们的发现表明神经调节蛋白作为一种作用于上皮细胞的间充质因子发挥功能。因此，神经调节蛋白的间充质表达可为间充质-上皮相互作用的生物学现象提供分子基础。这也对c-neu扩增影响癌肿瘤进展的分子机制具有启示意义。此外，在发育过程中神经调节蛋白在神经元细胞中表达。我们通过核糖核酸酶保护实验表明，神经调节蛋白的不同异构体在大脑中表达。因此，我们的数据表明神经调节蛋白在体内作为间充质因子和神经元因子具有双重作用。
