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.

器官必须有合适的大小和形状来完成它们在动物体内的作用。虽然尺寸是