Reverse-engineering mechanisms of neural circuit wiring in the fly visual system

果蝇视觉系统中神经回路布线的逆向工程机制

基本信息

项目摘要

Project Summary A central question in neuroscience is how neural circuits self-organize during development into functional structures. Neural circuit function relies on the precise specification of synapses, while alterations of synaptic connectivity are associated with numerous neurodevelopmental disorders. Seminal studies have identified mutations and molecular mechanisms that alter brain wiring. Yet, how this genetic information ultimately leads to self-assembly of neural circuits is poorly understood. What developmental programs lead to functional neuronal structures? What rules describe these programs? How do cells implement these rules? The Drosophila visual system represents a remarkable instance of the circuit self-assembly problem in the developing brain. The compound eye (consisting of ~800 ommatidia) is wired through a principle of “neural superposition” (NSP): 800 times six photoreceptors that see the same point in space, yet originate from six different ommatidia, find each other in the lamina and ‘wire together’ in synaptic cartridges. The correct sorting of photoreceptor growth cones results in a six-fold increase in light-gathering sensitivity without loss of spatial resolution. However, it is poorly understood how 4800 elongating growth cones stop at target cartridges with an astonishing accuracy of greater than 99%. In preliminary studies, we established the ability to use non-invasive, live-imaging based on multi-photon microscopy of intact and normally developing pupae to assay photoreceptor growth cone dynamics during NSP. Using this approach, we obtained the first quantitative measurements of individual growth cone dynamics throughout the entire NSP process and established that the complex program of NSP could arise from three simple local rules, which govern how growth cones anchor, elongate and stop in the lamina. Our work suggested the hypothesis that a cellular decision to stop wiring could arise from collective interactions with neighboring cells, and that these interactions could buffer biological variation, such as imperfect direction of growth cone elongation. To investigate collective stop decisions during NSP, we will: (Aim 1) experimentally determine potential times and places where growth cone fronts, backs and target cells could physically interact; (Aim 2) use these data to constrain computational models that systematically compare different models of stop rules; and (Aim 3) experimentally search for signatures of error propagation of NSP wiring in mutant conditions and identify molecular components that participate in the implementing the stop rule. 1
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 }}

STEVEN J ALTSCHULER其他文献

STEVEN J ALTSCHULER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('STEVEN J ALTSCHULER', 18)}}的其他基金

Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistance
GSK3 在结肠上皮稳态和耐药性中的系统水平作用
  • 批准号:
    9204413
  • 财政年份:
    2015
  • 资助金额:
    $ 37.57万
  • 项目类别:
Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistance
GSK3 在结肠上皮稳态和耐药性中的系统水平作用
  • 批准号:
    8996581
  • 财政年份:
    2015
  • 资助金额:
    $ 37.57万
  • 项目类别:
Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistance
GSK3 在结肠上皮稳态和耐药性中的系统水平作用
  • 批准号:
    8796044
  • 财政年份:
    2015
  • 资助金额:
    $ 37.57万
  • 项目类别:
Lung cancer heterogeneity and its impact on drug resistance.
肺癌异质性及其对耐药性的影响。
  • 批准号:
    8115195
  • 财政年份:
    2010
  • 资助金额:
    $ 37.57万
  • 项目类别:
Lung cancer heterogeneity and its impact on drug resistance.
肺癌异质性及其对耐药性的影响。
  • 批准号:
    8476204
  • 财政年份:
    2010
  • 资助金额:
    $ 37.57万
  • 项目类别:
Lung cancer heterogeneity and its impact on drug resistance.
肺癌异质性及其对耐药性的影响。
  • 批准号:
    8731633
  • 财政年份:
    2010
  • 资助金额:
    $ 37.57万
  • 项目类别:
Lung cancer heterogeneity and its impact on drug resistance.
肺癌异质性及其对耐药性的影响。
  • 批准号:
    8267104
  • 财政年份:
    2010
  • 资助金额:
    $ 37.57万
  • 项目类别:
Lung cancer heterogeneity and its impact on drug resistance.
肺癌异质性及其对耐药性的影响。
  • 批准号:
    7785211
  • 财政年份:
    2010
  • 资助金额:
    $ 37.57万
  • 项目类别:
Turnkey solution for image phenotype classification
图像表型分类的交钥匙解决方案
  • 批准号:
    8130804
  • 财政年份:
    2008
  • 资助金额:
    $ 37.57万
  • 项目类别:
Turnkey solution for image phenotype classification
图像表型分类的交钥匙解决方案
  • 批准号:
    7688099
  • 财政年份:
    2008
  • 资助金额:
    $ 37.57万
  • 项目类别:

相似海外基金

Defining the biological boundaries to sustain extant life on Mars
定义维持火星现存生命的生物边界
  • 批准号:
    DP240102658
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Discovery Projects
Advanced Multiscale Biological Imaging using European Infrastructures
利用欧洲基础设施进行先进的多尺度生物成像
  • 批准号:
    EP/Y036654/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Research Grant
Open Access Block Award 2024 - Marine Biological Association
2024 年开放获取区块奖 - 海洋生物学协会
  • 批准号:
    EP/Z532538/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Research Grant
NSF/BIO-DFG: Biological Fe-S intermediates in the synthesis of nitrogenase metalloclusters
NSF/BIO-DFG:固氮酶金属簇合成中的生物 Fe-S 中间体
  • 批准号:
    2335999
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
DESIGN: Driving Culture Change in a Federation of Biological Societies via Cohort-Based Early-Career Leaders
设计:通过基于队列的早期职业领袖推动生物协会联盟的文化变革
  • 批准号:
    2334679
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
Collaborative Research: The Interplay of Water Condensation and Fungal Growth on Biological Surfaces
合作研究:水凝结与生物表面真菌生长的相互作用
  • 批准号:
    2401507
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
REU Site: Modeling the Dynamics of Biological Systems
REU 网站:生物系统动力学建模
  • 批准号:
    2243955
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
Collaborative Research: Conference: Large Language Models for Biological Discoveries (LLMs4Bio)
合作研究:会议:生物发现的大型语言模型 (LLMs4Bio)
  • 批准号:
    2411529
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
Collaborative Research: Conference: Large Language Models for Biological Discoveries (LLMs4Bio)
合作研究:会议:生物发现的大型语言模型 (LLMs4Bio)
  • 批准号:
    2411530
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF-ANR MCB/PHY: Probing Heterogeneity of Biological Systems by Force Spectroscopy
合作研究:NSF-ANR MCB/PHY:通过力谱探测生物系统的异质性
  • 批准号:
    2412551
  • 财政年份:
    2024
  • 资助金额:
    $ 37.57万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了