Investigating Novel Transcriptional Mechanisms for Visual Neural Circuit Development and Function using Zebrafish
使用斑马鱼研究视觉神经回路发育和功能的新型转录机制
基本信息
- 批准号:10593144
- 负责人:
- 金额:$ 29.94万
- 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:2022-03-20 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAdultAffectAuditory systemAxonBehaviorBehavioralBioinformaticsBiological ModelsBrainCellsCenters of Research ExcellenceClinicalComplexCore FacilityDataDefectDevelopmentDiseaseElectroretinographyEmbryoEphrinsEtiologyEyeEye MovementsFunctional disorderGene ExpressionGene Expression ProfilingGenesGeneticGenetic ModelsGenetic Predisposition to DiseaseGenetic TranscriptionGenomicsGlutamatesGoalsHomeoboxHumanHuman GenomeInterneuronsKnock-outKnowledgeLinkMeasuresMediatingMentorsMicroscopyModelingMolecularMolecular GeneticsMorphologyMotorMusMutateNervous SystemNeural PathwaysNeuroanatomyNeurodevelopmental DisorderNeuronal DifferentiationNeuronsNeurophysiology - biologic functionOrthologous GenePatientsPharmacologyPhenotypePlayPositioning AttributePresynaptic TerminalsPrevention strategyReportingResearchResearch Project GrantsRetinal Ganglion CellsRodentRoleSaccadesSchizophreniaSensorySpecific qualifier valueStructureSymptomsTechniquesTectum MesencephaliTestingTimeVertebratesVisionVisualVisual SystemWorkZebrafishaxon guidancebehavior testbehavioral responsecell typecomorbiditycomparativediagnostic strategyexperimental studygene networkgenome wide association studyglutamatergic signalinghuman diseasein vivoinsightmRNA Expressionmutantneural circuitneurodevelopmentneuromechanismneurotransmissionnovelprogramsprotein expressionresponsesensory systemsuperior colliculus Corpora quadrigeminasynaptogenesistranscription factorvision developmentvision sciencevisual processingvisual stimulusvisual tracking
项目摘要
Project 003 (486): Investigating Novel Transcriptional Mechanisms for Visual Neural Circuit Development and
Function using Zebrafish, Bergeron, PL
PROJECT SUMMARY / ABSTRACT
Neuroanatomical and behavioral changes associated with neurodevelopmental disorders, such as eye tracking
dysfunction in schizophrenia, are caused by unknown genetic mechanisms. Identifying these critical gene
networks for sensory motor responsiveness in the visual system is one key to developing targeted early
diagnostic and preventative strategies for the symptoms of these disorders that make the world a difficult place
to navigate for those afflicted by them. My long-term goal is to characterize causative genetic mechanisms for
neurodevelopmental disorders-related phenotypes using zebrafish as a model system. This powerful genetic
model provides a unique opportunity as an easily accessible vertebrate with a comparatively “simple” nervous
system, rapid neurodevelopment, many orthologues of human disease-related genes, and defined and tractable
behavioral responses to visual stimuli. We can begin to study specific classes of neurons based on their
molecular identity and function from the moment that they are born in the embryo through adulthood in rapid
time compared to other vertebrate models. My previous work and that of others revealed for the first time the
molecular identity of key interneurons that mediate sensory processing and reflexive control in the mouse and
zebrafish auditory system. These neurons express the transcription factor Genomic Screen Homeobox 1 (Gsx1),
and I sought to determine the role that Gsx1 plays in the development of neural circuits for sensory processing
across the CNS. Upon examination of targeted gsx1 zebrafish mutants, we found profound defects in neuronal
differentiation and axon guidance in the developing visual system. Despite its documented expression in the
developing visual system in mouse and zebrafish, no research has been performed to date to examine the role
that Gsx1 plays in development and function of visual neural circuits. Given the importance of transcriptional
mechanisms for neural circuit development in sensory systems and the proposed ability to target key players in
these large gene networks to treat diseases, we seek to fill this gap in knowledge. Aim 1 of this proposal will
determine the consequences of mutating gsx1 on innate visually mediated behaviors and cell fate determination
in the zebrafish pretectum and the eye. The experiments described in Aim 2 will identify the cellular mechanisms
by which Gsx1 regulates arborization of axons in the pretectum that connect the eyes to the brain. We will be
able to perform these experiments and analyze and validate the large amount of data that will be generated
under the expert guidance of the Visual Function & Morphology Core, as well as the WVU Genomics Core Facility
and the Bioinformatics Core Facility. This research will provide insight into the complex genetic etiology of
neurodevelopmental disorders in which patients have comorbid defects in sensory processing. In addition, our
studies will provide an abundance of data that can be utilized to support future research projects that align well
with the development of visual function.
项目003(486):研究视觉神经回路发育和转录的新机制
使用斑马鱼、Bergeron、PL的功能
项目摘要/摘要
与神经发育障碍相关的神经解剖学和行为变化,如眼球跟踪
精神分裂症的功能障碍,是由未知的遗传机制引起的。识别这些关键基因
视觉系统中感觉运动反应的网络是早期形成靶向的关键之一
对这些使世界陷入困境的疾病症状的诊断和预防策略
为那些受他们折磨的人导航。我的长期目标是描述致病遗传机制的特征
以斑马鱼为模型系统的神经发育障碍相关表型。这种强大的基因
模型提供了一个独特的机会,因为它是一种容易接近的脊椎动物,具有相对简单的神经
系统,快速的神经发展,人类疾病相关基因的许多同源基因,并定义和处理
对视觉刺激的行为反应。我们可以开始研究特定类别的神经元,基于它们
从它们在胚胎中出生的那一刻起到成年后的分子身份和功能
与其他脊椎动物模型相比,时间更短。我之前的工作和其他人的工作第一次揭示了
介导小鼠感觉加工和反射控制的关键中间神经元的分子特性
斑马鱼的听觉系统。这些神经元表达转录因子基因组屏幕同源框1(Gsx1),
我试图确定Gsx1在感觉处理的神经回路发展中所起的作用
横跨中南欧。在对目标gsx1斑马鱼突变体的检查中,我们发现神经元存在严重缺陷。
视觉系统发育中的分化和轴突引导。尽管有文档记录了它在
在小鼠和斑马鱼身上开发视觉系统,到目前为止还没有进行任何研究来检验这种作用
Gsx1在视觉神经回路的发育和功能中发挥作用。考虑到转录的重要性
感觉系统中神经回路发育的机制和建议的针对关键角色的能力
这些庞大的基因网络用于治疗疾病,我们寻求填补这一知识空白。本提案的目标1将
确定突变的gsx1对先天视觉调节行为和细胞命运的影响
在斑马鱼的胎盘和眼睛里。目标2中描述的实验将确定细胞机制。
Gsx1通过它来调节大脑发育前连接眼睛和大脑的轴突的树枝形成。我们会的
能够执行这些实验并分析和验证将生成的大量数据
在视觉功能和形态核心以及西弗吉尼亚大学基因组核心设施的专家指导下
和生物信息学核心设施。这项研究将提供对复杂的遗传病因的洞察力。
神经发育障碍的患者在感觉处理方面有共同缺陷。此外,我们的
研究将提供丰富的数据,可以用来支持未来的研究项目,这些项目很好地结合在一起
随着视觉功能的发展。
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 }}
SADIE A BERGERON其他文献
SADIE A BERGERON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('SADIE A BERGERON', 18)}}的其他基金
Investigating Novel Transcriptional Mechanisms for Visual Neural Circuit Development and Function using Zebrafish
使用斑马鱼研究视觉神经回路发育和功能的新型转录机制
- 批准号:
10334879 - 财政年份:2022
- 资助金额:
$ 29.94万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 29.94万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 29.94万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 29.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 29.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 29.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)