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Symmetry breakage in the amphibian embryo

两栖动物胚胎的对称性破坏

基本信息

批准号：
55314144
负责人：
Professor Dr. Martin Blum
金额：
--
依托单位：
Fachgebiet Zoologie (190z)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/55314144?language=en
关键词：
Symmetry breakage amphibian embryo

项目摘要

Breakage of bilateral symmetry in vertebrates remains controversial: while a cilia-driven leftward flow is required in fish and mammals at gastrula/neurula stages, amphibian embryos show functionally relevant asymmetries already at cleavage. The ion flux model in frog postulates asymmetric segregation of low-molecular weight determinant(s) such as serotonin via an ion pump driven electrophoresis-like process through gap junctions. We recently showed that leftward flow is conserved in amphibians, and that inhibition of flow caused left-right (LR) defects. The main aims of this research proposal are (1) to determine if and how early asymmetries are connected to leftward flow at later stages; (2) to investigate whether or not early asymmetric determinants identified in frog act in mammalian left-right axis formation. Preliminary data suggest that these early determinants might be required for the development of a functional leftward flow in amphibian and mammalian embryos. Descriptive examinations will be performed to localize determinants during relevant embryonic stages. Functional experiments in frog, mouse and rabbit embryos will investigate H*-K*-ATPase, V-ATPase and serotonin in gain- and loss-of-function scenarios to unravel their roles with respect to flow characteristics (velocity and directionality) and laterality (marker genes and organ situs). The long-term goal of this study therefore is to develop a unifying model of vertebrate laterality determination.

脊椎动物双边对称性的破坏仍然存在争议：虽然在鱼类和哺乳动物的原肠胚/神经胚阶段需要纤毛驱动的纤毛流动，但两栖动物胚胎在卵裂时已经显示出功能相关的不对称性。青蛙中的离子通量模型假设低分子量决定簇（例如5-羟色胺）通过离子泵驱动的类突触过程通过间隙连接的不对称分离。我们最近发现，在两栖动物中，脑血流是保守的，而脑血流的抑制导致了左右（LR）缺陷。本研究计划的主要目的是（1）确定早期不对称性是否以及如何与后期的脑血流联系起来;（2）研究在青蛙中发现的早期不对称决定因素是否在哺乳动物左右轴形成中起作用。初步数据表明，这些早期的决定因素可能是需要在两栖动物和哺乳动物胚胎的功能性胚胎发育。将进行描述性检查，以定位相关胚胎阶段的决定因素。青蛙、小鼠和兔子胚胎的功能实验将研究H*-K*-ATP酶、V-ATP酶和血清素在功能获得和丧失情况下的作用，以阐明它们在流动特征（速度和方向性）和偏侧性（标记基因和器官部位）方面的作用。因此，本研究的长期目标是建立一个统一的脊椎动物侧化决定模型。