Matsunaga T, Davis J G, Greene M I
Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
DNA Cell Biol. 2001 Jun;20(6):307-19. doi: 10.1089/10445490152122424.
The erbB receptor family consists of erbB1/epidermal growth factor receptor, erbB2/neu, erbB3, and erbB4, all of which have been implicated in cell proliferation, differentiation, and survival in several tissues. In the nervous system, these family members can function in a trophic capacity for certain subpopulations of neurons and some types of non-neuronal cells. Vestibular sensory epithelial cells and vestibular ganglion neurons are derived from ectodermal otic placode and are essential components of the peripheral vestibular system, the sensory system for balance. Recent studies in mammals suggest that certain ligands of the epidermal growth factor receptor can induce proliferation of vestibular sensory epithelial cells. We now show that vestibular ganglion neurons and vestibular sensory epithelial cells express all four erbB receptors in adult rats. Cultured vestibular ganglion neurons also expressed all four erbB family members and were therefore used to analyze the effects of modulating erbB signaling on differentiated vestibular ganglion neurons. Transforming growth factor-alpha (a ligand for epidermal growth factor receptor) and sensory and motor neuron-derived factor (a ligand for erbB3 and erbB4) promoted vestibular ganglion neuron viability, whereas epidermal growth factor (another ligand for epidermal growth factor receptor) did not. Glial growth factor 2 (another ligand for erbB3 and erbB4) and an antibody that blocks erbB2/neu-mediated signaling inhibited vestibular ganglion neuron viability. Collectively, these observations indicate that erbB signaling regulates the viability of differentiated otic placode-derived cells in mammals and suggest that exogenous modulation of erbB signaling in peripheral vestibular tissues may prove therapeutically useful in peripheral vestibular disorders.
erbB受体家族由erbB1/表皮生长因子受体、erbB2/neu、erbB3和erbB4组成，所有这些受体都与多种组织中的细胞增殖、分化和存活有关。在神经系统中，这些家族成员可以对某些神经元亚群和一些非神经元细胞发挥营养作用。前庭感觉上皮细胞和前庭神经节神经元起源于外胚层耳基板，是外周前庭系统（平衡感觉系统）的重要组成部分。最近在哺乳动物中的研究表明，表皮生长因子受体的某些配体可以诱导前庭感觉上皮细胞增殖。我们现在发现，成年大鼠的前庭神经节神经元和前庭感觉上皮细胞表达所有四种erbB受体。培养的前庭神经节神经元也表达所有四种erbB家族成员，因此被用于分析调节erbB信号对分化的前庭神经节神经元的影响。转化生长因子-α（表皮生长因子受体的一种配体）以及感觉和运动神经元衍生因子（erbB3和erbB4的一种配体）可促进前庭神经节神经元的存活，而表皮生长因子（表皮生长因子受体的另一种配体）则无此作用。胶质生长因子2（erbB3和erbB4的另一种配体）以及一种阻断erbB2/neu介导信号的抗体可抑制前庭神经节神经元的存活。总的来说，这些观察结果表明，erbB信号调节哺乳动物中源自耳基板的分化细胞的存活，并提示在外周前庭组织中外源性调节erbB信号可能在治疗外周前庭疾病中具有治疗作用。
