Differentiation and function of intracardiac valve cells

心内瓣膜细胞的分化和功能

• 批准号: 394626537
• 负责人: Professor Dr. Achim Paululat
• 金额: --
• 依托单位: Arbeitsgruppe Zoologie-Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/394626537?language=en
• 关键词: Differentiation; function; intracardiac; valve; cells

Haemolymph flow in the Drosophila heart is controlled by intracardiac valves. The valve separates the posterior heart chamber from the anterior aorta and constitutes a simple gate-like structure in the larvae. The intracardiac valve is formed by only two individual cells, both of which display a unique histology with giant vesicular-like compartments, which we called valvosomes. Valvosomes are a characteristic feature of larval and adult Drosophila cardiac valves and are not formed in any other cardiomyocyte. In this project, we have two overarching goals. On the one hand, we want to analyse how exactly, on the molecular and cellular level, recycling endosomes, which are essential for the formation of valvosomes, are recruited towards valvosomes. Rab11 is the focus of interest here, as we identified Rab11-REs as essential for valvosome formation in the first application period. Our second goal is to analyze the importance of the cardiac valve cells for the pumping function of the heart. Here we study mutants with missing or defective cardiac valves and measure haemolymph flow with life markers in living animals. We consider the cardiac valve cells in flies as an evolutionary novelty, in which ancestral, fundamental endosomal pathways were modified to meet specific histological and physiological requirements. The canonical pathway for recycling proteins (RE pathway) is being "hijacked" in valve cells to generate a new and unique organelle, the valvosome. We will learn from our studies how histological and, eventually, anatomical novelties are generated during evolution by utilizing modules from an existing "construction kit".

果蝇心脏的血淋巴流动是由心内瓣膜控制的。瓣膜将心后腔与前主动脉分开，在幼虫体内形成简单的门状结构。心内瓣膜仅由两个单独的细胞组成，这两个细胞都具有独特的组织学，具有巨大的囊泡样腔室，我们称之为瓣小体。瓣膜体是幼虫和成年果蝇心脏瓣膜的特征，在任何其他心肌细胞中都不形成。在这个项目中，我们有两个首要目标。一方面，我们想分析在分子和细胞水平上，对瓣膜体形成至关重要的再循环内体是如何被招募到瓣膜体的。Rab11是这里关注的焦点，因为我们在第一个应用阶段确定了Rab11- res对瓣膜体形成至关重要。我们的第二个目标是分析心脏瓣膜细胞对心脏泵血功能的重要性。在这里，我们研究了心脏瓣膜缺失或缺陷的突变体，并在活体动物中使用生命标记物测量血淋巴流量。我们认为果蝇的心脏瓣膜细胞是一种进化上的新颖性，其中祖先的基本内体途径被修改以满足特定的组织学和生理要求。在瓣膜细胞中，典型的蛋白质循环途径（RE途径）被“劫持”，以产生一种新的独特的细胞器，即瓣膜体。我们将从我们的研究中学习如何通过利用现有的“构建套件”模块在进化过程中产生组织学和解剖学的新颖性。