Identifying mechanisms regulating collective cell migration

在所有多细胞动物中，集体细胞迁移是一个基本的过程，对于成年动物的生理功能，如伤口愈合和免疫细胞监测，对于胚胎发育和疾病包括转移，都是必不可少的。指导细胞集体迁移的机制包括感知外部指导线索(“输入”)和产生定向迁移的集体反应。这些信号可以是物理/机械、化学和/或电刺激，以指导集体运动。最近的研究结果强调，机械刺激和周围微环境的物理特性是细胞迁移过程中的决定性因素。然而，我们对这些因素如何促进活体内细胞集体迁移及其潜在机制的了解仍然非常有限。斑马鱼胚胎是研究体内细胞迁移的理想模式生物，因为胚胎是透明的，非常适合活体成像，不同胚胎之间转移细胞的可及性，以及从胚胎中分离细胞/组织进行体外工作的简便性。我们将重点研究中胚层组织，这是一种在脊椎动物中高度保守的细胞群，是早期胚胎发育的基础。精确的集体中胚层迁移失败会导致胚胎缺陷或死亡。我们将研究影响细胞集体取向和移动效率的微环境的机械线索和物理性质，以及这些信号是如何通过集体传递的。此外，我们还将研究物理屏障和粘附性表面对细胞迁移的影响。这些新的发现将有助于我们理解细胞迁移的一般原理，这些原理可以应用于生理和疾病相关的其他多细胞集体运动系统。

Collective cell migration is a fundamental process in all multicellular animals and is essential for physiological functions in adults such as wound healing and immune cell surveillance, for embryonic development and during disease including metastasis. Mechanisms guiding collectively migrating cells includes sensing external guidance cues ("inputs") and generating a collective response for directional migration. These signals can be physical/mechanical, chemical and/or electrical stimuli to guide collective movements. Recent findings emphasise that mechanical stimuli and physical properties of the surrounding microenvironment are decisive factors during cell migration. Yet, our knowledge of how these factors contribute to collective cell migration within living organisms and the underlying mechanisms remain very limited.The zebrafish embryo constitutes an ideal model organism to study cell migration in vivo, as the embryos are transparent and perfectly suited for live imaging, the accessibility of cells to be transferred between different embryos, and the ease to isolate cells/tissues from the embryo for in vitro work. We will focus our research on the mesendoderm tissue, which is a cell collective that is highly conserved in vertebrates and fundamental for early embryonic development. Failures of precise collective mesendoderm migration results in embryonic defects or death. We will investigate mechanical cues and physical properties of the microenvironment that influence orientation and movement efficiency of the cell collective, and how these signals are transduced through the collective. Further we will investigate how physical barriers and adhesive surfaces contribute to cell migration. These new findings will aid our understanding of general principles of cell migration that can be applied to other multicellular systems of collective motion in physiological and disease-related context.