How do glia remodel the nervous system?
神经胶质细胞如何重塑神经系统?
基本信息
- 批准号:10464236
- 负责人:
- 金额:$ 4.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-06 至 2024-10-05
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimalsApoptosisAstrocytesBiological AssayBiological MetamorphosisBiological ModelsCell CompartmentationCell Surface ReceptorsCellsCessation of lifeDataDefectDevelopmentDrosophila genusExcisionFailureGenesGeneticGoalsHumanImmunoglobulinsIndividualIntegral Membrane ProteinKnock-outKnowledgeLarvaLeadMammalsMediatingMethodsModelingMolecularNamesNatureNervous system structureNeuraxisNeuritesNeurodevelopmental DisorderNeurogliaNeuronsNeuropilPathway interactionsPhagocytesPhagocytosisPlayProcessProteinsRNA InterferenceResearchRoleSchizophreniaSignal TransductionSpecific qualifier valueSpecificityStereotypingSynapsesSystemTestingTurtlesVisual system structureWorkautism spectrum disordercell typeflyhuman diseasein vivoinsightknock-downneuronal cell bodyneuronal circuitryneurotransmissionnovelreceptorresponsesensory inputtooltranscriptomics
项目摘要
Project Summary
A common feature of nervous systems is that they are initially overpopulated with neurons and over-wired, initially
generating an excessive number of synaptic connections. This is followed by an essential period of remodeling
whereby a subset of extraneous neurons or synaptic connections are removed in order to optimize function in
the adult nervous system. The elimination of cells and pruning of synapses is a process coordinated by neurons
and glia. The selection of specific connections or cells for elimination seems to involve a conversation between
neurons and glia, and the clearance of debris from the nervous system is performed predominantly by phagocytic
glial cells. Previous research has highlighted that the nervous system uses a diversity of molecules and
mechanisms to identify engulfment targets, which appear to be context-specific. However, major gaps still exist
in our knowledge of how neurons identify themselves to be remodeled and how glial cells recognize these dying
or pruning neurons. Studying these processes can potentially lead us to a better understanding of mechanisms
underlying neurodevelopmental disorders such as Autism Spectrum Disorders and Schizophrenia. Our lab has
employed Drosophila as a model system for several reasons including the powerful genetic tools and the
stereotyped nature of one of its remodeling periods—metamorphosis. Through transcriptomic profiling in
phagocytic astrocytes, I identified the transmembrane immunoglobulin superfamily gene borderless. My
preliminary data suggests that Bdl is highly expressed in astrocytes during engulfment periods early in
metamorphosis. Interestingly, loss of both Borderless (Bdl) and the known engulfment receptor Draper (MEGF10
in mammals) resulted in strong suppression of astrocyte engulfment of synapses and neurites. Bdl has been
described to interact with a closely related protein named Turtle, and my preliminary data further suggests Turtle
is specifically localized to neurites and synapses, and excluded from the cell body (the only compartment of the
cell that astrocytes do not engulf). Turtle may therefore act as a molecular tag for astrocytes to recognize
appropriate engulfment targets. In Aim 1 of this study, I will characterize Bdl expression in astrocytes, explore
genetic interactions between Bdl and Draper, and determine which domains of Bdl are essential for engulfment
activity. In Aim 2, I will 1) define genetic interactions between Bdl, Turtle, and Draper, 2) determine the cell
autonomy of Bdl and Turtle in the remodeling of corazonin neurons and 3) determine the subcellular localization
of Turtle positing me to explore Turtle as a molecular tag for specifying neurites for engulfment. My work has the
potential to define two novel components of the astrocytic engulfment machinery, (Bdl and Turtle), explore how
they converge with Draper/MEGF10, and identify Turtle as a neurite/synapse-specific molecular tag that directly
directs astrocyte engulfment activity. This work will significantly advance our understanding of the molecular
basis of neuron-glia signaling during neuronal remodeling, which will be essential for us to understand and treat
neurodevelopmental disorders in humans.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Rachel Yvette De La Torre其他文献
Rachel Yvette De La Torre的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Rachel Yvette De La Torre', 18)}}的其他基金
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 4.68万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 4.68万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 4.68万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 4.68万 - 项目类别:
Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
- 批准号:
23KK0126 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 4.68万 - 项目类别:
Training Grant