Ciliary Neurotrophic Factor and Synaptic Components in Developing Chick Heart

9728881哈尔沃森是一种被称为细胞因子的分泌的生物活性分子，在胚胎发育过程中对各种组织的分化和成熟起着关键作用。确定这些细胞因子作用的分子机制对于全面了解神经系统发育是很重要的。最近描述的“神经生成性”细胞因子在发育中的神经和心血管系统中具有潜在的作用，到目前为止，这些作用在很大程度上还不清楚。本研究的总体目标是了解细胞因子睫状神经营养因子在心脏发育及其神经支配中的功能作用。将研究CNTF受体在发育过程中表达的重要机制，明确在副交感神经突触形成过程中心脏组织和培养心肌细胞中调节这些受体的分子机制，并确定CNTF对心脏关键突触成分的影响。该项目完成后，将解决三个基本问题。(1)CNTF受体水平的改变是否导致组织CNTF敏感性的改变？(2)CNTF受体在心脏中的调节机制(S)是什么？(3)CNTF在发育中的心房中是否参与副交感神经突触的形成？从长远来看，CNTF的下游基因和生化靶点以及相关的细胞因子在心脏中的作用将被确定。这些研究是首次确定CNTF受体在心血管系统中的表达和功能的一些研究。有了这些新的信息，我们将更好地了解在胚胎发育过程中调节神经心脏细胞对细胞因子的反应的机制，以及可能对成人维持这些功能重要的机制。

9728881 HALVORSEN The secreted, biologically active molecules called cytokines play key roles in the differentiation and maturation of a variety of tissues during embryonic development. It is important to determine the molecular mechanisms for these cytokine actions for a general understanding of nervous system development. The recently described "neuropoietic" cytokines have potential roles in the developing nervous and cardiovascular systems which are, as yet, largely undefined. The overall goal of this study is to understand the functional role of the cytokine ciliary neurotrophic factor (CNTF) in development of the heart and its innervation. The mechanisms important for expression of CNTF receptors during development will be investigated, the molecular mechanisms that regulate these receptors in heart tissue and in cultured myocytes during parasympathetic synapse formation will be defined, and the effects of CNTF on key synaptic components will be identified in the heart. Upon completion of the project three fundamental questions will have been addressed. (1) Does the change in CNTF receptor levels result in changes in tissue CNTF sensitivity? (2) What is (are) the mechanism(s) of regulation of CNTF receptors in heart? (3) Does CNTF play a role in parasympathetic synapse formation in the developing atria? Over the long term, downstream gene and biochemical targets of CNTF and related cytokine action in heart will be determined. These studies represent some of the first to define the expression and function of CNTF receptors in the cardiovascular system. With this new information we will have a better understanding of the mechanisms that regulate nerve-heart cell responses to cytokines during embryonic development and of mechanisms that may be important for maintenance of these functions in the adult.