Transcriptional Targets and Effectors of ZFP568, A Krab Zinc Finger Protein Required for Mammalian Convergent Extension

在胚胎发生过程中，组织和器官的形状获得需要协调的细胞重排。细胞重组如何帮助形成胚胎的一个优雅的例子是趋同扩展的过程。这一过程最早是在1895年被描述的，当时研究者观察到，随着胚胎的发育，少量插入鱼胚胎的针会向一个中心位置聚集，这些运动与胚胎从一个圆形的细胞球向一个具有前后极性的细长（或延伸）结构的转变有关。从那时起，更复杂的技术揭示了趋同延伸促进胚胎结构在各种模式生物和发育背景下的延伸。趋同延伸已经在青蛙、鱼类和苍蝇中得到了广泛的研究，但在哺乳动物中控制这一过程的细胞和分子机制却知之甚少。本项目主要研究小鼠kr<s:1> pel- associate - box （KRAB）锌指转录因子ZFP568的趋同扩展。本项目采用遗传和分子方法鉴定ZFP568的转录靶点和效应物。由于KRAB结构域蛋白是高等脊椎动物基因组中唯一存在的转录调节因子，因此研究结果将揭示这些生物特异性调节趋同扩展的分子事件。影响会聚伸展的条件会导致严重的胚胎畸形。因此，通过增加我们对控制早期哺乳动物形态发生机制的理解，这项研究将对发育生物学科学界产生广泛的影响。将为研究生和本科生提供科学教育和培训，作为项目的一个组成部分。PI和实验室还参与教育推广活动，以提高公众对发育生物学的认识。

The acquisition of shape by tissues and organs during embryogenesis requires coordinated cell rearrangements. An elegant example of how the reorganization of cells help to shape the embryo is the process of convergent extension. This process was first described in 1895, when investigators observed that pins sparsely inserted in fish embryos converged towards a central location as the embryo developed, and that these movements correlated with the transformation of the embryo from a rounded ball of cells to an elongated (or extended) structure with anterior-posterior polarity. Since then, more sophisticated techniques have revealed that convergent extension promotes elongation of embryonic structures in a variety of model organisms and developmental contexts. Convergent extension has been widely studied in frogs, fish and flies, but the cellular and molecular mechanisms that control this process in mammals are less well understood. This project focuses on the study of ZFP568, a Krüppel-Associated-Box (KRAB) Zinc finger transcription factor required for convergent extension in mouse. This project uses genetic and molecular approaches to identify the transcriptional targets and effectors of ZFP568. Because KRAB domain proteins are transcriptional regulators exclusively present in the genomes of higher vertebrates, results will shed light on the molecular events that regulate convergent extension specifically in these organisms. Conditions that affect convergent extension cause severe embryonic malformations. Therefore, by increasing our understanding of the mechanisms that control early mammalian morphogenesis, this study will have a broad impact on the developmental biology scientific community. Scientific education and training will be provided to graduate and undergraduate students as an integral part of the project. The PI and lab also participate in educational outreach activities that promote public awareness of Developmental Biology.