Gene-expression studies of epidermal Merkel cells

表皮默克尔细胞的基因表达研究

• 批准号: 6779347
• 负责人: Ellen A Lumpkin
• 金额: $ 33.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779347
• 关键词: biological signal transduction; electrophysiology; gene expression profiling; genetically modified animals; glutamates; immunocytochemistry; in situ hybridization; laboratory mouse; mechanoreceptors; membrane channels; method development; microarray technology; mixed tissue /cell culture; neurophysiology; neurotransmitter transport; somesthetic sensory cortex; touch

DESCRIPTION (provided by applicant): The long-term goal of this research is to elucidate the molecular basis of mechanotransduction by mammalian somatosensory receptor cells using the cutaneous Merkel cell-neurite complex as a model. Somatosensory mechanoreceptors mediate the senses of touch, pain and proprioception. The importance of these senses to human health is underscored by diseases that cause peripheral neuropathy such as rheumatoid arthritis, diabetes and acquired immunodeficiency syndrome. Because patients with peripheral neuropathy cannot feel injuries, even minor insults can lead to irreversible tissue damage and chronic pain. Although Merkel cells are conserved throughout vertebrate evolution, their function is unknown. Merkel cells have been proposed to be mechanoreceptors that transduce pressure and convey this information to the nervous system through synaptic transmission. Alternatively, Merkel cells may influence the activity of mechanosensory neurons through the release of neuromodulators. Finally, Merkel cells may affect the development of touch responsiveness, either by influencing the innervation patterns of sensory neurons or by directing neighboring epidermal cells to form specialized skin structures that are highly sensitive to touch. The objective of this application is to distinguish between these proposed functions by developing molecular and in vitro tools. First, we will use mouse DNA microarrays to identify gene-expression profiles of Merkel cells during and after maturation of the sense of cutaneous touch. Second, we will develop methods for studying ion channels and neurotransmitter release in dissociated Merkel cells. These in vitro methods will then be used to examine the roles of Merkel-cell-enriched molecules in signaling. By pinpointing molecules that may be essential for Merkel-cell signaling, these studies lay the groundwork for future investigation of the role of this epidermal cell in touch reception, and of the signals that initiate our perception of touch and pain. The proposed Specific Aims are: 1. Identify transcripts that are enriched in Merkel cells 2. Define the ionic conductances of dissociated Merkel cells 3. Characterize neurotransmitter release from Merkel cells in vitro

描述（由申请人提供）：本研究的长期目标是以皮肤默克尔细胞-神经突复合体为模型，阐明哺乳动物躯体感觉受体细胞的机械传导的分子基础。躯体感觉机械感受器介导触觉、疼痛和本体感觉。这些感觉对人类健康的重要性被引起周围神经病变的疾病所强调，如类风湿性关节炎、糖尿病和获得性免疫缺陷综合征。由于周围神经病变患者感觉不到损伤，即使是轻微的损伤也会导致不可逆的组织损伤和慢性疼痛。 虽然默克尔细胞在整个脊椎动物进化过程中是保守的，但它们的功能尚不清楚。默克尔细胞被认为是机械感受器，它可以感受压力并通过突触传递将此信息传递给神经系统。或者，默克尔细胞可以通过释放神经调节剂影响机械感觉神经元的活性。最后，默克尔细胞可能会影响触觉反应的发展，或者通过影响感觉神经元的神经支配模式，或者通过引导邻近的表皮细胞形成对触觉高度敏感的专门皮肤结构。 本申请的目的是通过开发分子和体外工具来区分这些提出的功能。首先，我们将使用小鼠DNA微阵列，以确定基因表达谱的默克尔细胞在成熟的皮肤触觉。第二，我们将开发研究游离默克尔细胞中离子通道和神经递质释放的方法。然后，这些体外方法将用于检查Merkel细胞富集分子在信号传导中的作用。通过精确定位可能对Merkel细胞信号传导至关重要的分子，这些研究为未来研究这种表皮细胞在触摸接收中的作用以及启动我们对触摸和疼痛的感知的信号奠定了基础。拟议的具体目标是： 1.鉴定在默克尔细胞中富集的转录物 2.定义解离的默克尔细胞的离子电导 3.表征体外默克尔细胞的神经递质释放