Mechanisms of Cell Communication in Animal Development

总结 我研究的主要目标是回答细胞和发育生物学中的一个主要问题： 细胞传递形态发生信号以在动物中产生组织模式。在发展领域内 细胞可以精确地调节信号交换的水平、时间和位置。这个控制中的任何偏差 机制导致发育畸形和疾病。大多数现有的模型提出， 蛋白质在细胞外空间中扩散以产生浓度梯度，并且这些细胞外 梯度调节靶细胞的生长、迁移和图案化。然而，我研究的一个主要焦点 程序是了解一个完全不同的机制-“直接传递”的信号，由专门的行动， 富含信号丝状伪足，称为细胞丝。我以前的工作探索并首先建立了功能角色 这种新的机制。我的工作表明细胞使用细胞素直接交换信号 并且细胞丝介导的信号传导对于细胞-细胞通信是必不可少的。我最近的工作主要集中在 成纤维细胞生长因子（FGF）是后生动物发育过程中的关键信号蛋白， 到细胞中。我们证明了FGF作为一种形态发生素， 在气管发育过程中的反应，FGF梯度是由蛋白酶依赖性切割控制的 FGF梯度是由细胞丝介导的信号传导形成的。最近，我们也有 发现了一个复杂的翻译后处理的FGF，可能控制其接触依赖的交换。我 目前的研究是利用强大的国家最先进的显微成像，生物化学，细胞 生物学和果蝇遗传学继续探索和研究控制细胞丝的机制， 介导的信号交换和信号分散。考虑到所有信号机制的保守性， 我们的研究将对人类发育和疾病的知识产生持久的影响。

SUMMARY The broad objective of my research is to answer a major question in cell and developmental biology: how do cells communicate morphogenetic signals to create tissue patterns in animals. Within a developmental field cells can precisely regulate the levels, timing and location of signal exchange. Any aberration in this control mechanism leads to developmental malformations and disease. Most existing models propose that signaling proteins diffuse in the extracellular space to generate concentration gradients, and that these extracellular gradients regulate growth, migration and patterning of target cells. However, a major focus of my research program is to understand a radically different mechanism - the ‘direct delivery’ of signals by specialized actin- rich signaling filopodia, named cytonemes. My previous work explored and first established the functional role of this novel mechanism in Drosophila. My work showed that cells use cytonemes to directly exchange signals and that cytoneme-mediated signaling is essential for cell-cell communication. My recent work is focused on Fibroblast Growth Factor (FGF), a key signaling protein in metazoan development, and its dispersion from cell to cell by cytonemes. We demonstrated that FGF acts as a morphogen that elicits concentration-dependent responses during tracheal development, that the FGF gradient is controlled by protease-dependent cleavage of the molecule, and that the FGF gradient is formed by cytoneme-mediated signaling. Recently, we also have uncovered a complex post-translation processing of FGF that may control its contact-dependent exchange. My current research is taking advantage of powerful state-of-the art microscopic imaging, biochemistry, cell biology and Drosophila genetics to continue to explore and investigate the mechanisms that control cytoneme mediated signal exchange and signal dispersion. Given the conservation of signaling mechanisms in all animals, our research will have a lasting impact on knowledge about development and disease in humans.