Development of retinal ganglion cell types
视网膜神经节细胞类型的发育
基本信息
- 批准号:9058640
- 负责人:
- 金额:$ 8.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-01 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAdultAffectAmazeAxonBiological AssayBrainCell Differentiation processCell ProliferationCell physiologyCellsCellular MorphologyCodeColorDNA-Binding ProteinsDevelopmentDiseaseEctopic ExpressionElectrodesElectroporationEmbryoExhibitsFutureGenesGlaucomaGoalsGrantImaging TechniquesIn VitroIndividualKnockout MiceKnowledgeLabelLeadLeftLifeMeasuresMitosisMitoticMolecularMolecular GeneticsMorphologyMotionMusNeuronsNormal CellOptic NerveOutcomes ResearchOutputPatternPhysical shapePhysiologicalPhysiologyProliferation MarkerPropertyProteinsProtocols documentationRecovery of FunctionReplacement TherapyRetinaRetinalRetinal DiseasesRetinal Ganglion CellsRoleSpecific qualifier valueSpecificitySpinal CordStagingStructureTechniquesTechnologyTestingTherapeuticTransgenic MiceViralVisualanatomical tracingbasebrain circuitrycell typedesignembryonic stem cellin vivoinsightisletmutantnerve stem cellneural circuitnovel strategiespreventprogenitorreceptive fieldrelating to nervous systemresearch studyresponserestorationstemsynaptogenesistranscription factorvisual information
项目摘要
DESCRIPTION (provided by applicant): The goal of this proposal is to understand the mechanisms used to create the circuitry of the mammalian retina. Specifically, experiments are aimed toward understanding the role of the transcription factors Islet-2 (Isl2) and specific AT-rich DNA-binding protein 2 (Satb2) in the specification of distinct types of retinal ganglion cells
(RGCs). RGCs are the output neurons of the retina and are affected in several retinal diseases such as glaucoma and optic nerve hypoplasias. There are numerous functional types of RGCs in the mammalian retina, each participating in a retinal circuit that encodes a specific aspect of the visual scene, such as motion, spatial patterns, or color. This functional specificity is derive from distinct RGC morphology and selective synapse formation with other cell types; however, how both are established during development remains unclear. Our experiments use a combination of mouse transgenic technology, in vivo physiological electrical recording and imaging techniques, and anatomical tracing. We focus on Isl2 and Satb2 because their expression is restricted to specific RGC classes, thereby suggesting a specific function. In Aim 1 we will determine which types of RGCs express Isl2 and Satb2 using both morphological and physiological criteria. Our hypothesis is that each TF specifies a common receptive field property of RGC types; for example, that Isl2+ RGCs are On and Off RGCs, while Satb2 RGCs may constitute direction selective cell types. Aim 1a is to determine Isl2 expression in mice expressing GFP in defined RGC subsets. Aims 1b and c together aim to classify all Isl2+ RGCs based on morphological and physiological criteria. In Aim 2 we will determine if Isl2 and Satb2 are necessary and sufficient for the RGCs to differentiate into their normal cell types by specifically removing Isl2 or Satb2 from the retina and by ectopically expressing them in developing RGCs. We will then determine the morphological and physiological properties of the resulting RGCs using a variety of physiological and morphological criteria. Our approach to study RGC differentiation will use our knowledge of the structure and function of different genetically-labeled RGC types to identify transcription factors that lead to their differentiation.
This will further our understanding of how different retinal circuits arise during development; thi in turn is likely to have practical benefits in understanding the consequences of diseases that affect RGC function. In addition, successful therapies for treating retinal diseases will depend on
the restoration of damaged visual circuits, making knowledge of the development of these circuits essential for designing therapeutic strategies and assessing functional recovery.
描述(由申请人提供):本提案的目标是了解用于创建哺乳动物视网膜回路的机制。具体地,实验旨在理解转录因子Islet-2(Isl 2)和特异性富含AT的DNA结合蛋白2(Satb 2)在不同类型的视网膜神经节细胞的特化中的作用
(RGC)。RGC是视网膜的输出神经元,并且在几种视网膜疾病如青光眼和视神经发育不全中受到影响。在哺乳动物视网膜中有许多功能类型的RGC,每一种都参与编码视觉场景的特定方面(例如运动、空间图案或颜色)的视网膜回路。这种功能特异性来源于不同的RGC形态和与其他细胞类型的选择性突触形成;然而,两者在发育过程中如何建立尚不清楚。我们的实验结合了小鼠转基因技术、体内生理电记录和成像技术以及解剖学示踪。我们专注于Isl 2和Satb 2,因为它们的表达仅限于特定的RGC类,从而表明特定的功能。 在目的1中,我们将使用形态学和生理学标准来确定哪种类型的RGC表达Isl 2和Satb 2。我们的假设是,每个TF指定一个共同的感受野性质的RGC类型,例如,Isl 2 + RGC是开和关的RGC,而Satb 2 RGC可能构成方向选择性细胞类型。目的1a是确定在限定的RGC亚组中表达GFP的小鼠中的Isl 2表达。目的1b和c一起旨在基于形态学和生理学标准对所有Isl 2 + RGC进行分类。 在目的2中,我们将通过从视网膜特异性去除Isl 2或Satb 2并通过在发育中的RGC中异位表达它们来确定Isl 2和Satb 2是否是RGC分化成其正常细胞类型所必需和足够的。然后,我们将使用各种生理和形态标准来确定所得到的RGC的形态和生理特性。 我们研究RGC分化的方法将利用我们对不同遗传标记的RGC类型的结构和功能的了解来鉴定导致其分化的转录因子。
这将进一步了解不同的视网膜回路在发育过程中是如何产生的;这反过来可能对理解影响RGC功能的疾病的后果有实际好处。此外,治疗视网膜疾病的成功疗法将取决于
修复受损的视觉回路,使这些回路的发展知识对于设计治疗策略和评估功能恢复至关重要。
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 }}
DAVID A FELDHEIM其他文献
DAVID A FELDHEIM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('DAVID A FELDHEIM', 18)}}的其他基金
Coding of auditory space in the mouse superior colliculus
小鼠上丘听觉空间的编码
- 批准号:
10361193 - 财政年份:2021
- 资助金额:
$ 8.5万 - 项目类别:
Coding of auditory space in the mouse superior colliculus
小鼠上丘听觉空间的编码
- 批准号:
10576405 - 财政年份:2021
- 资助金额:
$ 8.5万 - 项目类别:
Coding of auditory space in the mouse superior colliculus
小鼠上丘听觉空间的编码
- 批准号:
10840631 - 财政年份:2021
- 资助金额:
$ 8.5万 - 项目类别:
Multisensory integration in the mouse superior colliculus
小鼠上丘的多感觉整合
- 批准号:
10308501 - 财政年份:2020
- 资助金额:
$ 8.5万 - 项目类别:
Large-scale recording of visually-evoked activity in the mouse superior colliculus: functionality, topology, network properties and coding
小鼠上丘视觉诱发活动的大规模记录:功能、拓扑、网络属性和编码
- 批准号:
9181225 - 财政年份:2016
- 资助金额:
$ 8.5万 - 项目类别:
Classification of mouse RGC subtypes using large-scale multielectrode recording
使用大规模多电极记录对小鼠 RGC 亚型进行分类
- 批准号:
7642260 - 财政年份:2009
- 资助金额:
$ 8.5万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 8.5万 - 项目类别:
Research Grant