Nervous system regeneration, molecular basis in echinoderms

描述(由申请人提供)：缺乏有效的修复机制，包括有缺陷的纤维生长或有限的神经发生，是许多神经系统疾病或功能障碍的基础。因此，改善神经系统的愈合和/或再生过程的能力具有深远的治疗和经济后果。我们已经率先使用一种新的模型系统来研究神经系统的再生，棘皮动物海参。该物种可以在神经纤维的再生和神经再生的过程中再生其放射状神经索和肠道神经系统。棘皮动物与脊椎动物关系密切，因此，研究棘皮动物系统中的细胞和分子过程有助于阐明人类神经系统再生过程的机制。在目前的建议中，我们将重点放在与神经再生事件有关的几种蛋白质上。它们包括：(1)Orpin，一种来自海参的新蛋白质；(2)转铁蛋白，一种在许多脊索动物中发现但其功能仍不清楚的蛋白质；以及(3)两个众所周知的信号通路，Wnt和维甲酸，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涉及神经系统再生的各个步骤，包括神经细胞的分化和增殖、细胞凋亡和器官再生的神经依赖性。我们提出了包括体内和体外操作的实验，以确定蛋白质和mRNA的时空表达模式，以及蛋白质的功能。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，并将为人类如何实现这种再生提供重要线索。

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.