Genetic Regulation of Developmental and Regenerative Growth

项目总结/摘要 我们研究的总体目标是了解调节生长的机制：在细胞水平上， 个体细胞，器官水平和有机体水平。为了研究生长的规律，我们 研究了果蝇的成虫盘，成虫结构如翅膀的幼虫前体。 直到最近，我们工作的一个重要限制是我们几乎没有研究细胞异质性的工具。 这是体内生长调节的关键特征。单细胞转录组学使我们能够表征小的 对生长调节有重大影响的细胞亚群。通过将这种方法与实验相结合， 遗传学，我们现在可以研究一个关键方面的生长调节，涉及异型之间的相互作用， 细胞的小子集。 我们的目标是更好地了解再生生长的遗传调控。我们已经确定了一 基因调控网络是完全正常的发展，但对于再生至关重要 增长从我们的单细胞研究中鉴定出的其他基因指向在细胞中特异性表达的基因。 再生芽基的不同部分，可能调节再生的不同方面 包括增殖、细胞形状和细胞命运可塑性。我们将描述这些基因的功能。我们 他们还发现，椎间盘一部分的损伤和再生会影响椎间盘的发育。 椎间盘的其余部分以及远端器官。另一个目标是阐明这些长期- 范围现象 我们将研究离子通道在调节Hedgehog信号传导中的作用，以及细胞的生长和模式。 翼盘。我们将确定为什么具有更去极化膜电位的细胞存活 优选在翼盘的前室中。我们还将研究 机械敏感通道压电在生长调节中的作用。 最后，通过将我们的翼盘单细胞图谱与遗传筛选相结合，我们已经确定了许多 编码特征不佳的细胞表面蛋白和配体-受体对的基因，这些蛋白和配体-受体对可能在 发育以调节细胞存活、细胞增殖和平面细胞极性。我们将研究这些基因。

PROJECT SUMMARY/ABSTRACT The overall goal of our research is to understand the mechanisms that regulate growth: at the level of the individual cell, at the level of organs and at an organismal level. In order to study the regulation of growth, we have studied the imaginal discs of Drosophila, the larval precursors of adult structures such as the wing. Until recently, an important limitation to our work was that we had few tools to study the cellular heterogeneity that is a key feature of growth regulation in vivo. Single-cell transcriptomics allows us to characterize small subsets of cells that have a major impact on growth regulation. By combining this approach with experimental genetics, we can now study a key aspects of growth regulation that involves heterotypic interactions between small subsets of cells. We aim to obtain a better understanding of the genetic regulation of regenerative growth. We have identified a gene regulatory network that is entirely dispensable for normal development but is essential for regenerative growth. Additional genes identified from our single-cell studies point to genes that are specifically expressed in different portions of the regeneration blastema and which likely regulate different aspects of regeneration including proliferation, cell shape and cell-fate plasticity. We will characterize the function of these genes. We have also found that damage and regeneration of one portion of the disc can impact the development of the remainder of the disc and also distant organs. Another goal is to elucidate the mechanistic basis of these long- range phenomena. We will examine the role of ion channels in regulating Hedgehog signaling and the growth and patterning of the of the wing disc. We will determine why cells with a more depolarized membrane potential survive preferentially in the anterior compartment of the wing disc. We will also study the properties of the mechanosensitive channel Piezo in growth regulation. Finally, by combining our single cell atlas of the wing disc with a genetic screen, we have identified many genes encoding poorly-characterized cell-surface proteins and ligand-receptor pairs that likely function during development to regulate cell survival, cell proliferation and planar cell polarity. We will study these genes.