In Vivo Analysis of TrkB Signaling During Sympathetic Nervous System Development and Neuroblastoma Pathogenesis

交感神经系统发育和神经母细胞瘤发病机制中 TrkB 信号传导的体内分析

基本信息

  • 批准号:
    8873369
  • 负责人:
  • 金额:
    $ 24.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-02-01 至 2017-01-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The molecular and cellular interactions that orchestrate the patterning of the vertebrate peripheral nervous system have yet to be fully elucidated. Upon delamination from the neural tube, trunk neural crest cells destined to form the vertebral chain of sympathetic ganglia migrate ventrally to the vicinity of the dorsal aorta where they aggregate and condense to form the primary chain of sympathetic ganglia composed of differentiated sympathetic neurons and precursor cells. Failure of the neural crest cells to properly migrate and differentiate may result in birth defects and lead to neuroblastoma, a pediatric tumor. of the peripheral nervous system that arises from sympatho-adrenal lineages of the neural crest. Unfortunately, the lack of information about normal development of the sympathetic nervous system and how mis-regulation of signals transform the normal neuroblast to neuroblastoma has severely limited early neuroblastoma detection and treatment, making this disease often fatal in infants. We propose to study sympathetic nervous system development and neuroblastoma pathogenesis using state- of-the-art in vivo imaging in living avian embryos. We discovered a novel role for TrkB signaling during sympathetic neurogenesis, which strikingly has recently been associated with aggressive neuroblastomas. We hypothesize that TrkB signals regulate the plasticity and invasive ability of the neural crest during sympathetic nervous system development at a critical time period when the early transformation from normal neuroblast to neuroblastoma occurs. To test this hypothesis we will determine the functional role of TrkB signaling in sympathetic nervous system development and develop a quail embryo model for neuroblastoma pathogenesis. Quail embryos allow transplantation and visualization of individual human neuroblastoma cell behaviors, a technique pioneered in our laboratory. We recently discovered that human neuroblastoma cells transplanted into the avian embryo follow host neural crest pathways and do not form tumors. The success of this proposal will have a direct impact on neural development and neuroblastoma cancer by providing: (i) critical information on the in vivo role of TrkB signaling during sympathetic neurogenesis and in the early transition from normal neuroblast to neuroblastoma; (ii) an in vivo model to rapidly assay the plasticity and invasiveness of neuroblastoma cells and response to potential inhibitors.
 描述(由申请人提供):协调脊椎动物外周神经系统模式的分子和细胞相互作用尚未完全阐明。在从神经管分层时,注定形成交感神经节的椎链的主干神经嵴细胞向腹侧迁移到背主动脉附近,在那里它们聚集并凝聚以形成由分化的交感神经元和前体细胞组成的交感神经节的初级链。神经嵴细胞不能正常迁移和分化可能导致出生缺陷,并导致神经母细胞瘤,一种儿科肿瘤。来自神经嵴的交感肾上腺谱系的周围神经系统的。不幸的是,缺乏关于交感神经系统正常发育以及信号的错误调节如何将正常神经母细胞转化为神经母细胞瘤的信息,严重限制了早期神经母细胞瘤的检测和治疗,使得这种疾病在婴儿中往往是致命的。我们建议使用最先进的活禽胚胎体内成像技术研究交感神经系统发育和神经母细胞瘤发病机制。我们发现了TrkB信号在交感神经发生过程中的新作用,这一作用最近与侵袭性神经母细胞瘤密切相关。我们推测TrkB信号在交感神经过程中调节神经嵴的可塑性和侵袭能力, 在从正常神经母细胞到神经母细胞瘤的早期转化发生的关键时期,系统发育。为了验证这一假设,我们将确定TrkB信号传导在交感神经系统发育中的功能作用,并建立神经母细胞瘤发病机制的鹌鹑胚胎模型。鹌鹑胚胎允许移植和可视化的个人人类神经母细胞瘤细胞的行为,在我们的实验室开创的技术。我们最近发现,人类神经母细胞瘤细胞移植到鸟类胚胎遵循宿主神经嵴通路,不形成肿瘤。该提案的成功将通过提供以下内容对神经发育和神经母细胞瘤癌症产生直接影响:(i)关于TrkB信号传导在交感神经发生期间和在从正常神经母细胞到神经母细胞瘤的早期转变中的体内作用的关键信息;(ii)快速测定神经母细胞瘤细胞的可塑性和侵袭性以及对潜在抑制剂的响应的体内模型。

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 }}

PAUL KULESA其他文献

PAUL KULESA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('PAUL KULESA', 18)}}的其他基金

Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma
研究交感神经系统发育与神经母细胞瘤之间的关系
  • 批准号:
    10658015
  • 财政年份:
    2023
  • 资助金额:
    $ 24.75万
  • 项目类别:
A novel platform to enhance single cell interrogation of nervous system development
增强神经系统发育单细胞询问的新平台
  • 批准号:
    10678917
  • 财政年份:
    2022
  • 资助金额:
    $ 24.75万
  • 项目类别:
Application of Gabriella Miller Kids First Pediatric Research Data to a Predictive Model of Neuroblastoma
Gabriella Miller Kids First 儿科研究数据在神经母细胞瘤预测模型中的应用
  • 批准号:
    10757183
  • 财政年份:
    2022
  • 资助金额:
    $ 24.75万
  • 项目类别:
A novel platform to enhance single cell interrogation of nervous system development
增强神经系统发育单细胞询问的新平台
  • 批准号:
    10757179
  • 财政年份:
    2022
  • 资助金额:
    $ 24.75万
  • 项目类别:
Application of Gabriella Miller Kids First Pediatric Research Data to a Predictive Model of Neuroblastoma
Gabriella Miller Kids First 儿科研究数据在神经母细胞瘤预测模型中的应用
  • 批准号:
    10193881
  • 财政年份:
    2021
  • 资助金额:
    $ 24.75万
  • 项目类别:
In Vivo Analysis of TrkB Signaling During Sympathetic Nervous System Development and Neuroblastoma Pathogenesis
交感神经系统发育和神经母细胞瘤发病机制中 TrkB 信号传导的体内分析
  • 批准号:
    8995712
  • 财政年份:
    2015
  • 资助金额:
    $ 24.75万
  • 项目类别:
In Vivo Analysis of the Mechanisms of Neural Crest Migration
神经嵴迁移机制的体内分析
  • 批准号:
    8321015
  • 财政年份:
    2008
  • 资助金额:
    $ 24.75万
  • 项目类别:
In Vivo Analysis of the Mechanisms of Neural Crest Migration
神经嵴迁移机制的体内分析
  • 批准号:
    8134840
  • 财政年份:
    2008
  • 资助金额:
    $ 24.75万
  • 项目类别:
In Vivo Analysis of the Mechanisms of Neural Crest Migration
神经嵴迁移机制的体内分析
  • 批准号:
    7532831
  • 财政年份:
    2008
  • 资助金额:
    $ 24.75万
  • 项目类别:
In Vivo Analysis of the Mechanisms of Neural Crest Migration
神经嵴迁移机制的体内分析
  • 批准号:
    7900330
  • 财政年份:
    2008
  • 资助金额:
    $ 24.75万
  • 项目类别:

相似海外基金

Role of hypothalamic MC4R in glucose homeostasis via a novel neuroendocrine circuit involving the kidneys and adrenal glands
下丘脑 MC4R 通过涉及肾脏和肾上腺的新型神经内分泌回路在葡萄糖稳态中的作用
  • 批准号:
    10454300
  • 财政年份:
    2021
  • 资助金额:
    $ 24.75万
  • 项目类别:
Role of hypothalamic MC4R in glucose homeostasis via a novel neuroendocrine circuit involving the kidneys and adrenal glands
下丘脑 MC4R 通过涉及肾脏和肾上腺的新型神经内分泌回路在葡萄糖稳态中的作用
  • 批准号:
    10666539
  • 财政年份:
    2021
  • 资助金额:
    $ 24.75万
  • 项目类别:
Role of hypothalamic MC4R in glucose homeostasis via a novel neuroendocrine circuit involving the kidneys and adrenal glands
下丘脑 MC4R 通过涉及肾脏和肾上腺的新型神经内分泌回路在葡萄糖稳态中的作用
  • 批准号:
    10296199
  • 财政年份:
    2021
  • 资助金额:
    $ 24.75万
  • 项目类别:
Role of hypothalamic MC4R in glucose homeostasis via a novel neuroendocrine circuit involving the kidneys and adrenal glands
下丘脑 MC4R 通过涉及肾脏和肾上腺的新型神经内分泌回路在葡萄糖稳态中的作用
  • 批准号:
    10854123
  • 财政年份:
    2021
  • 资助金额:
    $ 24.75万
  • 项目类别:
Interaction of adrenal glands and liver in canine hepatocellular carcinoma
犬肝细胞癌中肾上腺和肝脏的相互作用
  • 批准号:
    20H03139
  • 财政年份:
    2020
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Role of dendritic cells in adrenal glands of healthy and arthritic rats
树突状细胞在健康和关节炎大鼠肾上腺中的作用
  • 批准号:
    235438724
  • 财政年份:
    2013
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Research Grants
Role of neural cell adhesion molecules in structural and functional remodeling of fetal adrenal glands
神经细胞粘附分子在胎儿肾上腺结构和功能重塑中的作用
  • 批准号:
    20591305
  • 财政年份:
    2008
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Search for the novel etiology in disorders of sex development (DSD) caused by abnormalities of adrenal glands and gonads.
寻找由肾上腺和性腺异常引起的性发育障碍 (DSD) 的新病因。
  • 批准号:
    16086202
  • 财政年份:
    2004
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Effects of endocrine disrupters on function of thyroid gland, adrenal glands and gonads
内分泌干​​扰物对甲状腺、肾上腺和性腺功能的影响
  • 批准号:
    11839003
  • 财政年份:
    1999
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Roles of Thyroid and Adrenal glands in the regulation of hypothalamo-hypophysial-ovarian axis in the rat.
甲状腺和肾上腺在大鼠下丘脑-垂体-卵巢轴调节中的作用。
  • 批准号:
    06660375
  • 财政年份:
    1994
  • 资助金额:
    $ 24.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了