ABERRANT NEURAL AND CARDIAC DEVELOPMENT IN MICE LACKING THE ERBB4 NEUREGULIN RECEPTOR
ABERRANT NEURAL AND CARDIAC DEVELOPMENT IN MICE LACKING THE ERBB4 NEUREGULIN RECEPTOR
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DOI：
10.1038/378390a0
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发表时间：
1995-11-23
期刊：
影响因子：
64.8
通讯作者：
LEMKE, G
中科院分区：
文献类型：
--
作者：
GASSMANN, M;CASAGRANDA, F;LEMKE, G
各种体外研究表明，ErbB 4（HER 4）是神经调节蛋白的受体，神经调节蛋白是一个密切相关的蛋白质家族，涉及神经和肌肉发育以及乳腺上皮分化和致癌转化的调节剂（1-3）。在这里，我们证明，ErbB 4是一个重要的在体内调节器的心肌分化和轴突的指导在中枢神经系统（CNS）。缺乏ErbB 4的小鼠在胚胎发育中期死于心室中心肌小梁的发育中止。他们还显示显着的变化，在中枢神经系统中的后脑的神经支配，这是一致的限制性表达的ErbB 4基因在菱球3和5。ErbB 4和神经调节蛋白基因突变体的心脏表型的相似性表明ErbB 4在心脏中作为神经调节蛋白受体发挥作用;然而，这些突变体的后脑表型的差异与新的ErbB 4配体在CNS中的作用一致。
VARIOUS in vitro studies have suggested that ErbB4 (HER4) is a receptor for the neuregulins, a family of closely related proteins implicated as regulators of neural and muscle development, and of the differentiation and oncogenic transformation of mammary epithelia(1-3). Here we demonstrate that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS). Mice lacking ErbB4 die during mid-embryogenesis from the aborted development of myocardial trabeculae in the heart ventricle. They also display striking alterations in innervation of the hindbrain in the CNS that are consistent with the restricted expression of the ErbB4 gene in rhombomeres 3 and 5. Similarities in the cardiac phenotype of ErbB4 and neuregulin gene mutants suggest that ErbB4 functions as a neuregulin receptor in the heart; however, differences in the hindbrain phenotypes of these mutants are consistent with the action of a new ErbB4 ligand in the CNS.