Mechanisms of cellular morphogenesis that coordinate signaling during tissue patterning

项目摘要 我们研究计划的长期目标是了解和识别细胞形状的机制 促进从局部细胞-细胞通讯事件中出现组织范围模式的动力学。这个 干扰信号对基因和细胞行为的不正确时空诱导可能导致 发展中的灾难性错误。因此，重要的是要了解信号机制是如何采取 放置在细胞或相邻细胞的水平上在较大的组织长度尺度上进行协调以实现坚固 模式和支持组织的动态平衡。细胞丝，或信号丝足，是一种富含肌动蛋白的长细胞。 允许细胞与远处的其他细胞进行物理交互并向其发出信号的突起。蜂窝 像细胞素这样的突起已经被证明在许多发育过程中发挥作用，包括Spot 以及条纹图案化、肢体图案化、干细胞壁龛维护和神经板图案化。尽管如此， 对调控细胞素特异性形成和行为的一般机制知之甚少。 我们有兴趣了解这些突起是如何在细胞骨架水平上受到调节的 机制，并作为细胞范围和组织范围信号状态的一个组成部分。要解决这个问题 问题，我们使用果蝇背胸毛的斑点图案作为 模型系统。在刚毛形成过程中，细胞丝从胸腺上皮细胞的基面延伸到 促进长距离、凹槽介导的侧向抑制。利用我们在果蝇模型系统方面的优势 遗传学和定量活显微镜，在未来五年里，我们的目标包括了解 细胞素的形成受到调控，尤其是在Notch介导的侧向抑制信号的下游。在……里面 与此类似，我们的目标是了解细胞素活性如何促进细胞和组织的异质性 促进及时形成有条不紊的格局。这些研究不仅将产生有价值的细胞 关于细胞素的具体调控的生物学知识，但也将阐明基本 协调不同长度比例的图案的机构。

Project Summary The long-term goal of our research program is to understand and identify the mechanisms of cell shape dynamics that facilitate the emergence of tissue-wide patterns from local cell-cell communication events. The incorrect spatial and temporal induction of genes and cell behaviors by perturbed signaling can lead to catastrophic errors in development. Therefore, it is critical to understand how signaling mechanisms that take place at the level of a cell or adjacent cells are coordinated across larger tissue length scales to achieve robust patterns and support tissue homeostasis. Cytonemes, or signaling filopodia, are long actin-rich cellular protrusions that allow cells to physically interact with, and signal to, other cells at a distance. Cellular protrusions like cytonemes have been shown to play a role in many developmental processes, including spot and stripe patterning, limb patterning, stem cell niche maintenance, and neural plate patterning. Despite this, relatively little is known about the general mechanisms that regulate cytoneme-specific formation and behavior. We are interested in understanding how these protrusions are regulated both at the level of cytoskeletal mechanisms, and as an integrated part of the cell-wide and tissue-wide signaling states. To address this problem, we use the spot pattern of bristles on the dorsal thorax of the fruit fly Drosophila melanogaster as a model system. During bristle patterning, cytonemes extend from the basal surface of thoracic epithelial cells to facilitate long-range, Notch-mediated, lateral inhibition. Leveraging our strengths in Drosophila model systems genetics and quantitative live microscopy, over the next five years our goals include understanding how the formation of cytonemes are regulated, especially downstream of Notch-mediated lateral inhibition signaling. In parallel, we aim to understand how cytoneme activity contributes to cell and tissue heterogeneities that facilitate the timely formation of well-organized patterns. These studies will not only yield valuable cell biological knowledge about the specific regulation of cytonemes, but will also elucidate fundamental mechanisms that coordinate patterning across length scales.