Gene-expression studies of epidermal Merkel cells

表皮默克尔细胞的基因表达研究

基本信息

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
项目类别：
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

项目摘要

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使用皮肤默克尔细胞-神经突复合物作为模型，阐明哺乳动物体感受体细胞机械转导的分子基础。体感机械感受器介导触觉、疼痛和本体感觉。类风湿性关节炎、糖尿病和获得性免疫缺陷综合症等引起周围神经病变的疾病凸显了这些感觉对人类健康的重要性。由于周围神经病变患者感觉不到受伤，即使是轻微的伤害也可能导致不可逆的组织损伤和慢性疼痛。尽管默克尔细胞在脊椎动物进化过程中一直保守，但其功能尚不清楚。默克尔细胞被认为是机械感受器，可以传导压力并通过突触传递将信息传递到神经系统。或者，默克尔细胞可能通过释放神经调节剂来影响机械感觉神经元的活动。最后，默克尔细胞可能通过影响感觉神经元的神经支配模式或引导邻近的表皮细胞形成对触摸高度敏感的特殊皮肤结构来影响触摸反应能力的发展。该应用的目的是通过开发分子和体外工具来区分这些提议的功能。首先，我们将使用小鼠 DNA 微阵列来识别默克尔细胞在皮肤触觉成熟期间和之后的基因表达谱。其次，我们将开发研究离解默克尔细胞中离子通道和神经递质释放的方法。这些体外方法将用于检查富含默克尔细胞的分子在信号传导中的作用。通过查明默克尔细胞信号传导可能必需的分子，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感知触摸和疼痛的信号奠定了基础。拟议的具体目标是： 1. 识别默克尔细胞中富集的转录本 2. 定义分离默克尔细胞的离子电导 3. 表征默克尔细胞体外神经递质释放