Identifying mechanisms regulating collective cell migration

集体细胞迁移是所有多细胞动物中的基本过程，并且对于成年人的生理功能（例如伤口愈合和免疫细胞监视）、胚胎发育和疾病（包括转移）期间是必不可少的。引导集体迁移的细胞的机制包括感测外部引导线索（“输入”）和产生定向迁移的集体响应。这些信号可以是物理/机械、化学和/或电刺激，以引导集体运动。最近的研究结果强调，周围微环境的机械刺激和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生物体内的集体细胞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型生物，因为胚胎是透明的，非常适合活体成像，细胞在不同胚胎之间转移的可及性，以及易于从胚胎中分离细胞/组织用于体外工作。我们将把我们的研究重点放在中内胚层组织，这是一个细胞集体，是高度保守的脊椎动物和早期胚胎发育的基础。中内胚层的精确集体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方向和运动效率的微环境的机械线索和物理特性，以及这些信号如何通过集体转导。此外，我们将研究物理屏障和粘附表面如何促进细胞迁移。这些新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背景下的集体运动的其他多细胞系统。

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.