Lee K F, Simon H, Chen H, Bates B, Hung M C, Hauser C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037, USA.
Nature. 1995 Nov 23;378(6555):394-8. doi: 10.1038/378394a0.
The receptor erbB2/neu is a member of the epidermal growth factor receptor (EGFR or erbB) family that also includes erbB3 and erbB4. Amplification of the erbB2/neu gene is found in many cancer types and its overexpression is correlated with a poor prognosis for breast and ovarian cancer patients. Investigation of the biology of erbB2 led to the identification of a family of ligands termed neuregulins which included the neu-differentiation factors, the heregulins, a ligand with acetylcholine-receptor-inducing activity and glial growth factor. Several lines of evidence suggest that heterodimerization of erbB2 with other erbB receptors is required for neuregulin signalling. Here we investigate the developmental role of erbB2 in mammalian development in mice carrying an erbB2 null allele. We find that mutant embryos die before E11, probably as a result of dysfunctions associated with a lack of cardiac trabeculae. Development of cranial neural-crest-derived sensory ganglia was markedly affected. DiI retrograde tracing revealed that the development of motor nerves was also compromised. Our results demonstrate the importance of erbB2 in neural and cardiac development.
受体erbB2/neu是表皮生长因子受体（EGFR或erbB）家族的成员，该家族还包括erbB3和erbB4。erbB2/neu基因的扩增在许多癌症类型中都有发现，其过表达与乳腺癌和卵巢癌患者的不良预后相关。对erbB2生物学特性的研究导致了一类称为神经调节蛋白的配体家族的鉴定，其中包括神经分化因子、heregulin、一种具有诱导乙酰胆碱受体活性的配体和神经胶质生长因子。几条证据表明，erbB2与其他erbB受体的异源二聚化是神经调节蛋白信号传导所必需的。在这里，我们研究了携带erbB2无效等位基因的小鼠中erbB2在哺乳动物发育中的作用。我们发现突变胚胎在E11之前死亡，可能是由于与缺乏心脏小梁相关的功能障碍。颅神经嵴衍生的感觉神经节的发育受到显著影响。DiI逆行追踪显示运动神经的发育也受到损害。我们的结果证明了erbB2在神经和心脏发育中的重要性。
