Mechanisms of cellular morphogenesis that coordinate signaling during tissue patterning

项目概要 我们研究计划的长期目标是了解和确定细胞形状的机制 促进局部细胞间通讯事件出现组织范围模式的动力学。的 通过扰动信号传导对基因和细胞行为的不正确的空间和时间诱导可能导致 发展过程中的灾难性错误。因此，了解信号传导机制如何发挥作用至关重要。 位于细胞或相邻细胞水平的位置在更大的组织长度尺度上协调，以实现稳健 模式和支持组织稳态。细胞质，或信号丝状伪足，是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相互作用并向其发送信号的突起。蜂窝网络 像细胞线这样的突起已被证明在许多发育过程中发挥作用，包括斑点 以及条纹图案、肢体图案、干细胞生态位维持和神经板图案。尽管如此， 对于调节细胞因子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传导状态的一个组成部分。为了解决这个问题 问题，我们使用果蝇 Drosophila melanogaster 背胸部的鬃毛斑点图案作为 模型系统。在刷毛图案化过程中，细胞线从胸上皮细胞的基底表面延伸到 促进长程、Notch 介导的侧向抑制。利用我们在果蝇模型系统方面的优势 遗传学和定量活体显微镜，在接下来的五年里，我们的目标包括了解如何 细胞因子的形成受到调节，尤其是Notch介导的侧抑制信号传导的下游。在 与此同时，我们的目标是了解细胞因子活性如何影响细胞和组织的异质性 有利于及时形成井然有序的格局。这些研究不仅会产生有价值的细胞 有关细胞因子特定调节的生物学知识，但也将阐明基本原理 跨长度尺度协调图案的机制。

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.