Mechanisms Underlying Type II Cadherin Guided Assembly of Retinal Circuits
II 型钙粘蛋白引导视网膜电路组装的潜在机制
基本信息
- 批准号:10317067
- 负责人:
- 金额:$ 39.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAnatomyAtlasesAxonBiological AssayBiological ModelsBipolar NeuronBrainBrain regionCRISPR/Cas technologyCadherinsCell Adhesion MoleculesCell CommunicationCellsChimeric ProteinsClustered Regularly Interspaced Short Palindromic RepeatsCodeComplexDefectDetectionDevelopmentDiseaseEnsureEtiologyEyeEye diseasesFamilyGenesGeneticGenetic TechniquesGoalsIndividualInjectionsInterneuronsKnowledgeLeadLocationLogicMediatingMethodsMolecularMolecular ProfilingNervous system structureNeuraxisNeuritesNeuronsNosePatternPhysiologicalPositioning AttributeProcessProteinsRetinaRetinal Ganglion CellsRoleSeriesSignal TransductionSpecific qualifier valueSpecificityStudy modelsSynapsesSystemTestingTo specifyTranslatingVisionVisualaxon guidancebasecombinatorialdifferential expressionexperimental studyextracellulargain of functionganglion cellgenetic approachin uteroin vivoinnovationinsightmutantnervous system disorderneural circuitneurodevelopmentneuronal patterningnovelpostsynapticrelating to nervous systemretinal neuronsegregationstarburst amacrine cellsynaptogenesistoolvisual information
项目摘要
In the eye, complex retinal circuits are wired together for precise neural computation. The diverse but precise
wiring between interneurons and retinal ganglion cells serve as the structural basis for circuit processing of
different visual features. These parallel circuits are wired up precisely, as defects may lead to several eye
diseases and neurological disorders. To investigate the mechanisms behind how diverse neuronal types
precisely integrate into distinct parallel retinal circuits, we developed methods that allow for targeted genetic
access of the unique On-Off direction-selective circuit, which conveys direction-selectivity signals, as the ideal
model system. Our previous studies now position us to examine the role of Type II Cadherins (Cdhs) in
assembling this circuit as individual proteins or in combinations. We showed that two Cdhs, Cdh9 and Cdh8,
instruct parallel ON and OFF bipolar cell input to ON vs. OFF sublaminae of the ON-OFF direction-selective
circuit, thus allowing precise segregation of ON and OFF channels. However, the molecular mechanisms
underlying this assembly remain elusive. To investigate the molecular mechanisms underlying the differential
functions of Cdh9 vs. Cdh8, we will perform a series of anatomical and functional analyses. We will identify the
specific portion of the cadherin molecule, extracellular versus intracellular domains, that are responsible for
their distinct functions, as well as the specific timing of their actions in forming synapses between bipolar cells
and ganglion cells. We also found that Cdh9 from bipolar neurons heterophilically recognizes the two closely-related Cdhs, Cdh6 and Cdh10, from postsynaptic Ventral-pointing ON-OFF direction-selective ganglion cells
(ooDSGCs) and starburst amacrine cells (SACs). We will use this established genetic system to reveal how
combinatorial Cdhs act together to wire up parallel direction-selective circuits. We will examine genetically and
functionally how Cdh6-9-10 single, double, and triple combinations pattern the Ventral-ooDSGC interaction
with SACs. To further expand our understanding of the combinatorial cadherin code in neuronal patterning, we
will test the role of Cdh11, which is identified as a Nasal-pointing ooDSGC enriched gene through molecular
profiling. Thus, we will generate new molecularly and genetically targeted methods to examine the roles of
Cdh11 and its closely related Cdh8 in the wiring of Nasal-pointing direction-selective circuits. Furthermore, we
established an in utero injection system to ectopically introduce individual Type II Cdhs onto Ventral-ooDSGCs or Nasal-ooDSGCs to pinpoint combinatorial Cdhs in regulating DS-circuit patterning. Collectively,
our studies seek to reveal how Cdh combinations control the formation of parallel but distinct DS circuits.
Comprehensive studies on Type II Cdh function would be a major advance for a long-standing question in
mammalian neural development. These studies will be a major step forward in understanding how multiple
genes interact to specify the wiring of complex neural circuits. The identified mechanisms will have significant
relevance to selective circuit wiring throughout the central nervous system.
在眼睛里,复杂的视网膜回路被连接在一起进行精确的神经计算。多样但精确的
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)
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{{ truncateString('Xin Duan', 18)}}的其他基金
MAPPING RETINOTECTAL CIRCUITS FOR VISUAL-EVOKED INNATE BEHAVIORS
绘制视觉诱发先天行为的视网膜环路
- 批准号:
10300917 - 财政年份:2021
- 资助金额:
$ 39.16万 - 项目类别:
MAPPING RETINOTECTAL CIRCUITS FOR VISUAL-EVOKED INNATE BEHAVIORS
绘制视觉诱发先天行为的视网膜环路
- 批准号:
10463759 - 财政年份:2021
- 资助金额:
$ 39.16万 - 项目类别:
MAPPING RETINOTECTAL CIRCUITS FOR VISUAL-EVOKED INNATE BEHAVIORS
绘制视觉诱发先天行为的视网膜环路
- 批准号:
10676764 - 财政年份:2021
- 资助金额:
$ 39.16万 - 项目类别:
Mechanisms Underlying Type II Cadherin Guided Assembly of Retinal Circuits
II 型钙粘蛋白引导视网膜电路组装的潜在机制
- 批准号:
9886125 - 财政年份:2020
- 资助金额:
$ 39.16万 - 项目类别:
Mechanisms Underlying Type II Cadherin Guided Assembly of Retinal Circuits
II 型钙粘蛋白引导视网膜电路组装的潜在机制
- 批准号:
10541108 - 财政年份:2020
- 资助金额:
$ 39.16万 - 项目类别:
Administrative Supplement to NEI - EY030138
NEI 行政补充 - EY030138
- 批准号:
10669952 - 财政年份:2020
- 资助金额:
$ 39.16万 - 项目类别:
Mechanisms Underlying Type II Cadherin Guided Assembly of Retinal Circuits
II 型钙粘蛋白引导视网膜电路组装的潜在机制
- 批准号:
10077558 - 财政年份:2020
- 资助金额:
$ 39.16万 - 项目类别:
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