Control of developmental timing and body size in Drosophila

果蝇发育时间和体型的控制

• 批准号: 8526476
• 负责人: MICHAEL Brendan O'CONNOR
• 金额: $ 34.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526476
• 关键词: Activins; Address; Adolescent; Affect; Age; Animals; Attention; Belief; Binding; Biological Metamorphosis; Body Size; Cells; Competence; Coupled; Cues; Development; Developmental Process; Drosophila genus; Ecdysone; Ecdysterone; Endocrine; Enzymes; Event; Gene Expression; Genetic; Gland; Growth Factor; Health; Hormones; Human; Indium; Insect Control; Insecta; Learning; Lepidoptera; Ligands; Light; MAP Kinase Gene; Mammals; Mediating; Mediator of activation protein; Metabolic; Molecular; Molting; Neurons; Neuropeptides; Neurosecretory Systems; Nuclear Receptors; Nucleic Acid Regulatory Sequences; Nutritional; Organism; Peptides; Physiologic pulse; Process; Production; Puberty; Receptor Protein-Tyrosine Kinases; Signal Transduction; Staging; Steroid biosynthesis; Steroids; System; Testing; Time; Transcriptional Regulation; Vertebrates; Vesicle; Work; activating transcription factor; hormone control mechanism; imaging modality; interest; programs; public health relevance; receptor; reproductive; research study; response; steroid hormone; trafficking

DESCRIPTION (provided by applicant): Proper development of all multi-cellular organisms requires not only correct spatial control of cellular interactions, but also correct timing of specific gene expression programs during development. Altering the timing of many developmental processes can significantly affect an animals final body size, reproductive ability and ageing. In insects, timing of developmental transitions, i.e. molting and metamorphosis, is mediated by 20-hydroxyecdysone (20E), a small circulating lipophilic steroid hormone that binds to and activates transcription factors of the nuclear receptor superfamily. Although the genetic hierarchy that controls responses to 20E has received considerable attention, little is presently known about mechanisms that control the timing of hormone production and its release. In this proposal we will determine how prothoraciotropic hormone, a peptide released from neurons that innervate the prothoracic gland (PGs) control hormone production and release. In aim 1 we will determine when the PG cells receive PTTH signals and what regulates their competence to do so. In aim 2 we will characterize additional upstream and downstream inputs that regulate PTTH signaling through the receptor tyrosine kinase Torso. Of particular interest is to determine if the PTTH ligand processing is required for PTTH signaling and if PKC, PLC and the IP3 receptor, contribute to PTTH signaling in Drosophila and how their activity is coupled to Torso activation. In aim 3, we will identify key transcriptional control elements in the regulatory regions of the ecdysone biosynthetic enzymes phm, dib and spookier, in order to learn how PTTH signals regulate ecdysone production. In aim4 we will use genetic studies and imaging methods to test the hypothesis that, contrary to present beliefs, release of ecdysone from the prothoracic gland during the metamorphic molt is a vesicle mediated process stimulated by PTTH. Impact on human health: In humans, a major developmental transition involving steroid hormones takes place as adolescents acquire sexual maturity. This transition is also controlled by a neuropeptide signal in conjunction with nutritional and metabolic cues, although little is presently known about how these signals are integrated to time the transition appropriately. The studies described here will help identify basic molecular programs that control developmental transitions and thereby provide a paradigm for understanding how these processes might be regulated in vertebrates including humans. In addition these studies will provide a new understanding of how steroid hormones are released from endocrine cells. PUBLIC HEALTH RELEVANCE: The studies described here will help identify basic molecular programs that regulate steroid hormone production and secretion in insects. Since related developmental transitions and steroid release mechanisms occur in many organisms, including humans, this work will provide a paradigm for understanding how different steroidogenic regulatory cues are integrated by the neuroendocrine circuit to control development.

描述（由申请人提供）：所有多细胞生物的正确发育不仅需要细胞相互作用的正确空间控制，还需要发育过程中特定基因表达程序的正确计时。改变许多发育过程的时间可以显着影响动物最终的体型、繁殖能力和衰老。在昆虫中，发育转变（即蜕皮和变态）的时机是由 20-羟基蜕皮酮 (20E) 介导的，20E 是一种小型循环亲脂性类固醇激素，可结合并激活核受体超家族的转录因子。尽管控制 20E 反应的遗传等级受到了相当多的关注，但目前对控制激素产生及其释放时间的机制知之甚少。在本提案中，我们将确定促前胸腺激素（一种从支配前胸腺（PG）的神经元释放的肽）如何控制激素的产生和释放。在目标 1 中，我们将确定 PG 细胞何时接收 PTTH 信号以及什么调节它们的能力。在目标 2 中，我们将描述通过受体酪氨酸激酶躯干调节 PTTH 信号传导的其他上游和下游输入。特别令人感兴趣的是确定 PTTH 信号传导是否需要 PTTH 配体加工，以及 PKC、PLC 和 IP3 受体是否有助于果蝇中的 PTTH 信号传导，以及它们的活性如何与躯干激活相耦合。在目标 3 中，我们将鉴定蜕皮激素生物合成酶 phm、dib 和 spookier 调节区域中的关键转录控制元件，以了解 PTTH 信号如何调节蜕皮激素的产生。在目标 4 中，我们将使用遗传研究和成像方法来检验以下假设：与目前的看法相反，在变态蜕皮过程中前胸腺释放蜕皮激素是由 PTTH 刺激的囊泡介导的过程。对人类健康的影响：在人类中，随着青少年性成熟，涉及类固醇激素的重大发育转变发生。这种转变也受到神经肽信号以及营养和代谢线索的控制，尽管目前人们对如何整合这些信号以适当地调整转变时间知之甚少。这里描述的研究将有助于确定控制发育转变的基本分子程序，从而为理解如何在包括人类在内的脊椎动物中调节这些过程提供范例。此外，这些研究将为内分泌细胞如何释放类固醇激素提供新的认识。 公共健康相关性：此处描述的研究将有助于确定调节昆虫类固醇激素产生和分泌的基本分子程序。由于相关的发育转变和类固醇释放机制发生在包括人类在内的许多生物体中，这项工作将为理解神经内分泌回路如何整合不同的类固醇生成调节线索来控制发育提供一个范例。

项目成果

Transcriptional control of steroid biosynthesis genes in the Drosophila prothoracic gland by ventral veins lacking and knirps.

• DOI: 10.1371/journal.pgen.1004343
• 发表时间: 2014-06
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Danielsen ET;Moeller ME;Dorry E;Komura-Kawa T;Fujimoto Y;Troelsen JT;Herder R;O'Connor MB;Niwa R;Rewitz KF
• 通讯作者: Rewitz KF

The Drosophila Zinc Finger Transcription Factor Ouija Board Controls Ecdysteroid Biosynthesis through Specific Regulation of spookier.

• DOI: 10.1371/journal.pgen.1005712
• 发表时间: 2015-12
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Komura-Kawa T;Hirota K;Shimada-Niwa Y;Yamauchi R;Shimell M;Shinoda T;Fukamizu A;O'Connor MB;Niwa R
• 通讯作者: Niwa R

Vesicle-Mediated Steroid Hormone Secretion in Drosophila melanogaster.

• DOI: 10.1016/j.cell.2015.10.022
• 发表时间: 2015-11-05
• 期刊: Cell
• 影响因子: 64.5
• 作者: Yamanaka N;Marqués G;O'Connor MB
• 通讯作者: O'Connor MB

Neuroendocrine control of Drosophila larval light preference.

• DOI: 10.1126/science.1241210
• 发表时间: 2013-09-06
• 期刊: Science (New York, N.Y.)
• 作者: Yamanaka N;Romero NM;Martin FA;Rewitz KF;Sun M;O'Connor MB;Léopold P
• 通讯作者: Léopold P

Current Topics in Developmental Biology. Developmental timing. Preface.

发育生物学的当前主题。

• DOI: 10.1016/b978-0-12-396968-2.09990-5
• 发表时间: 2013
• 期刊: Current topics in developmental biology
• 作者: Rougvie,AnnE;O'Connor,MichaelB
• 通讯作者: O'Connor,MichaelB