Coordination of Growth and Form in the Embryonic Salivary Gland and Trachea

胚胎唾液腺和气管生长和形态的协调

• 批准号: 10453482
• 负责人: Deborah J Andrew
• 金额: $ 54.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-05 至 2022-11-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453482
• 关键词: Affect; Animals; Apical; Binding; Biological Assay; Biological Models; Biological Process; Caliber; Cell Count; Cell Shape; Cell Size; Cell surface; Cells; ChIP-seq; Coupled; Couples; Cues; DNA; DNA Binding; Defect; Development; Differentiation and Growth; Dimensions; Drosophila genus; Embryo; Embryonic Development; Enhancers; Environment; Event; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Gases; Gene Expression; Gene Proteins; Genes; Genetic Transcription; Growth; Human; Individual; Learning; Length; Ligands; Link; Mitotic; Modeling; Molecular; Morphogenesis; Morphology; Nuclear; Nuclear Protein; Organ; Organ Size; Pathway interactions; Physiological; Positioning Attribute; Process; Production; Proteins; Regulation; Ribosomal Proteins; Ribosomes; Role; Salivary Glands; Secretory Cell; Shapes; Signal Pathway; Signal Transduction; System; Testing; Tissues; Trachea; Transcription Initiation Site; Translations; Tube; Work; cell growth; fitness; migration; mutant; organ growth; promoter; receptor; response; rib bone structure

Organs must be the right size and shape to fulfill their roles in the animal. Although size is intimately linked to organ function, we know almost nothing about how size control is coupled to organ differentiation during embryonic development. In the proposed work, we focus on how developmental growth and differentiation are coordinated in the Drosophila embryo, an ideal system for revealing the underlying molecular and cellular mechanisms. We have discovered that the nuclear protein Ribbon (Rib) is required for growth and morphogenesis of two distinct organs in the Drosophila embryo and that Rib promotes growth by two different mechanisms in the two tissues. In rib mutants, both salivary gland and tracheal cells are only ~50% the size of WT, and both organs have additional morphological defects. In the salivary gland, Rib binds genes encoding most of the >80 ribosomal protein genes, suggesting that Rib promotes growth in this tissue by increasing the translational capacity of its large secretory cells. In the trachea, Rib binds components of the Tor growth control pathway and other growth genes. We propose the model that Rib couples Tor signaling to FGF signaling to coordinate growth and directional migration in response to both developmental and physiological cues. In this proposal, we test these ideas and we ask how Rib independently regulates morphogenetic factors, specifically those that function at the apical cell surface to control tube elongation. We begin by testing the idea that Rib upregulates ribosomal protein gene expression in the salivary gland to increase translation in these professional secretory cells and we test the model that the small cell size observed in the salivary glands of rib mutants is a ribosome deficiency problem. We then test the model that Rib coordinates growth in the trachea by linking the FGF and Tor signaling pathways to build a system that links growth to migratory cues. We also explore the role of other candidate growth regulators. We determine if a candidate Rib target that is bound by Rib in both the SG and trachea also regulates growth and we determine if Rib affects levels of protein translation. Finally, we ask how Rib coordinates growth and morphogenesis by identifying the co-activators relevant to each process and by characterizing the functions of a subset of target genes linked to cell shape change.

器官必须具有正确的大小和形状，以履行其在动物中的作用。虽然尺寸是 与器官功能密切相关，我们几乎不知道大小控制是如何与器官功能联系在一起的。 胚胎发育过程中的器官分化。在建议的工作中，我们专注于如何 发育生长和分化在果蝇胚胎中是协调的， 揭示潜在的分子和细胞机制的系统。我们已经发现 核蛋白Ribbon（Rib）是两种不同的哺乳动物生长和形态发生所必需的。 Rib通过两种不同的机制促进果蝇胚胎的生长， 两个组织。在rib突变体中，唾液腺和气管细胞的大小仅为 WT，并且两个器官都具有额外的形态学缺陷。在唾液腺里， 编码大多数>80核糖体蛋白基因的基因，表明Rib促进生长 通过增加其大分泌细胞的翻译能力。在气管里， Rib结合Tor生长控制途径和其他生长基因的组分。我们提出 Rib将Tor信号传导耦合到FGF信号传导以协调生长和定向生长的模型， 迁移是对发育和生理线索的反应。在本提案中，我们测试 这些想法，我们问肋骨如何独立调节形态发生因子，特别是 在顶端细胞表面起作用以控制管伸长的那些。我们开始测试 Rib上调唾液腺核糖体蛋白基因表达 翻译在这些专业的分泌细胞，我们测试的模型，小细胞大小 在Rib突变体的唾液腺中观察到的是核糖体缺陷问题。然后我们测试 Rib通过连接FGF和Tor信号来协调气管中的生长的模型 建立一个将生长与迁徙线索联系起来的系统。我们还探讨了其他的作用。 候选生长调节剂。我们确定是否在两种情况下都被Rib绑定的候选Rib目标 SG和气管也调节生长，我们确定肋骨是否影响蛋白质水平 翻译.最后，我们问肋骨如何协调生长和形态发生，通过确定 与每个过程相关的共激活剂，并通过表征目标的子集的功能， 与细胞形状改变有关的基因