Nervous system regeneration, molecular basis in echinoderms

神经系统再生，棘皮动物的分子基础

基本信息

批准号：
8434295
负责人：
JOSE E GARCIA-ARRARAS
金额：
$ 44.4万
依托单位：
UNIVERSITY OF PUERTO RICO RIO PIEDRAS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434295
关键词：
Accounting Address Amaze Antibodies Apoptosis Biological Models Calcium-Binding Proteins Caring Cell Death Cell Differentiation process Cell Proliferation Cell physiology Cells Cessation of life Chordata Cues Data Dementia Dependency Disease Economics Enteral Enteric Nervous System Epithelial Cells Epithelium Event Exhibits Expressed Sequence Tags Fiber Follow-Up Studies Foxes Genes Growth Healed Holothuria Human In Vitro Injury Intestines Laboratories Mesentery Messenger RNA Microarray Analysis Modeling Molecular Muscle National Institute of Neurological Disorders and Stroke Natural regeneration Nerve Nerve Fibers Nerve Regeneration Nerve Tissue Nervous System Trauma Nervous system structure Neurodegenerative Disorders Neuronal Differentiation Neurons Organism Outcome Patients Pattern Play Process Proteins Relative (related person)Research Personnel Role Sea Cucumbers Signal Pathway Signaling Pathway Gene Solutions Spinal cord injury Stress Structure of radial nerve System Testing Therapeutic Tissues Training Transcript Tretinoin Underrepresented Minority Vertebrates base cost graduate student healing improved in vivo nervous system development nervous system disorder neurogenesis novel organ regeneration overexpression precursor cell protein function public health relevance regenerative repaired research study undergraduate student

项目摘要

DESCRIPTION (provided by applicant): The lack of an efficient repair mechanism that includes defective fiber growth or limited neurogenesis is the basis for many diseases or malfunctions of the nervous system. Consequently, the capacity to improve healing and/or regeneration processes in the nervous system has profound therapeutic, as well as economical consequences. We have pioneered the use of a novel model system to study nervous system regeneration, The echinoderm Holothuria glaberrima. This species can regenerate both its radial nerve cord and enteric nervous system in a process that includes re-growth of nerve fibers and neurogenesis. Echinoderms are closely related to vertebrates, thus, the study of cellular and molecular processes in this system can serve to illuminate the mechanisms involved in nervous system regenerative processes in humans. In the present proposal we focus on several proteins that are involved in nervous regenerative events. These include: (1) Orpin, a novel protein characterized from the holothurian, (2) melanotransferrin, a protein found in many chordates but whose function remains elusive, and (3) two well-known signaling pathways, Wnt and retinoic acid, that have been shown to be associated with nervous system development in other species. The study of these molecules will address various steps in the regeneration of the nervous system, including nerve cell differentiation and proliferation, apoptosis and nerve-dependency of organ regeneration. We propose experiments that include in vivo and in vitro manipulations to determine the protein and mRNA temporal and spatial expression patterns, as well as the protein function. The expected results will help understand the molecular mechanisms that underlie the amazing regeneration of the nervous system in holothurians and will provide important cues on how this regeneration might be achieved in humans.

描述（由申请人提供）：缺乏有效的修复机制（包括纤维生长缺陷或神经发生有限）是许多神经系统疾病或功能障碍的基础。因此，改善神经系统愈合和/或再生过程的能力具有深远的治疗和经济效果。我们率先使用一种新型模型系统来研究神经系统再生，即棘皮动物海参。该物种可以在包括神经纤维重新生长和神经发生的过程中再生其桡神经索和肠神经系统。棘皮动物与脊椎动物密切相关，因此，对该系统中的细胞和分子过程的研究可以有助于阐明人类神经系统再生过程中涉及的机制。在本提案中，我们重点关注参与神经再生事件的几种蛋白质。其中包括：(1) Orpin，一种源自海参的新型蛋白质；(2) 黑转铁蛋白，一种在许多脊索动物中发现的蛋白质，但其功能仍然难以捉摸；(3) 两种众所周知的信号传导途径，Wnt 和视黄酸，已被证明与其他物种的神经系统发育有关。对这些分子的研究将解决神经系统再生的各个步骤，包括神经细胞分化和增殖、细胞凋亡以及器官再生的神经依赖性。我们提出的实验包括体内和体外操作以确定蛋白质和 mRNA 的时间和空间表达模式以及蛋白质功能。预期的结果将有助于理解海参神经系统惊人再生的分子机制，并将为如何在人类中实现这种再生提供重要线索。