Coordination of Growth and Form in the Embryonic Salivary Gland and Trachea
Coordination of Growth and Form in the Embryonic Salivary Gland and Trachea
批准号:
10453482
负责人:
Deborah J Andrew
金额:
$54.91万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-08-05 至 2022-11-04
关键词:
AffectAnimalsApicalBindingBiological AssayBiological ModelsBiological ProcessCaliberCell CountCell ShapeCell SizeCell surfaceCellsChIP-seqCoupledCouplesCuesDNADNA BindingDefectDevelopmentDifferentiation and GrowthDimensionsDrosophila genusEmbryoEmbryonic DevelopmentEnhancersEnvironmentEventFibroblast Growth FactorFibroblast Growth Factor ReceptorsGasesGene ExpressionGene ProteinsGenesGenetic TranscriptionGrowthHumanIndividualLearningLengthLigandsLinkMitoticModelingMolecularMorphogenesisMorphologyNuclearNuclear ProteinOrganOrgan SizePathway interactionsPhysiologicalPositioning AttributeProcessProductionProteinsRegulationRibosomal ProteinsRibosomesRoleSalivary GlandsSecretory CellShapesSignal PathwaySignal TransductionSystemTestingTissuesTracheaTranscription Initiation SiteTranslationsTubeWorkcell growthfitnessmigrationmutantorgan growthpromoterreceptorresponserib bone structure
中文摘要
器官的大小和形状必须合适,才能在动物体内发挥它们的作用。尽管大小是
与器官功能密切相关的是,我们几乎不知道大小控制是如何与器官功能相关联的
胚胎发育过程中的器官分化。在提议的工作中,我们重点关注如何
在果蝇胚胎中,发育生长和分化是协调的,这是理想的
用于揭示潜在的分子和细胞机制的系统。我们发现
认为核蛋白带(Rib)是生长和形态发生所必需的两种截然不同的
果蝇胚胎中的器官和肋骨通过两种不同的机制促进生长
这两张纸巾。在肋骨突变体中,唾液腺和气管细胞的大小都只有
WT,而且两个器官都有额外的形态缺陷。在唾液腺中,肋骨结合
编码大多数核糖体蛋白基因的基因,表明肋骨促进生长
通过增加其大型分泌细胞的翻译能力在这种组织中。在气管里,
RIB结合了Tor生长控制途径的组件和其他生长基因。我们建议
RIB将Tor信号与成纤维细胞生长因子信号耦合以协调生长和定向的模型
对发育和生理信号作出反应的迁徙。在这个提案中,我们测试
这些想法和我们问RIB如何独立地调节形态发生因子,特别是
在顶端细胞表面起作用以控制管子伸长的那些。我们首先测试
肋骨上调唾液腺核糖体蛋白基因表达的想法
在这些专业的分泌细胞中进行翻译,我们测试了小细胞大小的模型
在肋骨突变体的唾液腺中观察到核糖体缺乏的问题。然后我们测试
肋骨通过连接成纤维细胞生长因子和Tor信号来协调气管内生长的模型
建立一个将增长与迁徙线索联系起来的系统的途径。我们还探讨了其他角色
候选增长监管者。我们确定由RIB绑定的候选RIB目标是否在
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,我们问肋骨是如何通过识别
与每个进程相关的共激活剂,并通过表征目标子集的功能
与细胞形状改变有关的基因。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
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海外基金