Role of inductive signals released by nasal mesenchyme and brain in controlling terminal nerve development and GnRH-1 neuronal migration

鼻间充质和大脑释放的诱导信号在控制终末神经发育和 GnRH-1 神经元迁移中的作用

基本信息

  • 批准号:
    9590917
  • 负责人:
  • 金额:
    $ 44.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-07 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

Summary GnRH-1 neurons are essential for sexual competence and fertility in vertebrates. During development, GnRH-1 neurons migrate from the embryonic nasal area into the brain, where they eventually localize to the hypothalamus to control the release of gonadotropins from the pituitary gland. Defects in GnRH-1 migration cause various forms of hypogonadotropic hypogonadism (HH) in humans, which is characterized by delayed pubertal onset, hypogonadism and infertility. HH in humans manifests clinically as either Kallmann syndrome (KS) or normosmic idiopathic HH (nIHH). In KS, HH is associated with deficiencies in the sense of smell. This association led to the long-held, prevailing view that the GnRH-1 neurons migrate from the nose to the hypothalamus along the axons of olfactory and vomeronasal sensory neurons. However, our recent data suggest that the migration of the GnRH-1 neurons to the hypothalamus may rely on the terminal nerve (TN), which is formed by neurons distinct from the olfactory and vomeronasal sensory neurons. KS and nIHH are often associated with several non-reproductive anomalies including craniofacial defects, cleft/lip palate and dental agenesis. Craniofacial mesenchymal tissues play a pivotal role in controlling neuronal development and differentiation in the nasal area. Dysregulations in Sonic Hedgehog signaling can cause various craniofacial abnormalities, including holoprosencephaly, midline defects, cleft lip/palate and dental agenesis. Expression of genes downstream of hedgehog critically depend on interactions with the glioblastoma gene products (Gli) family of transcription factors (Gli1, Gli2, and Gli3). By analyzing whole exome sequencing data from a cohort of 580 patients affected by HH and KS, we identified candidate rare Gli3 point mutations. Our central hypothesis is that loss of Gli3 alters the expression of inductive signals, released by nasal mesenchyme and brain, which are necessary for terminal nerve and GnRH-1 neuronal development. We propose that this mechanism underlies KS and nIHH in humans. By exploiting mouse genetics, cutting edge imaging, human whole genome sequencing, organotypic cultures and site direct mutagenesis experiments, we will discover new mechanisms by which inductive factors modulate the hedgehog-Gli signaling system to control formation of a functional GnRH-1 system in vertebrates. Successful completion of our study will generate crucial clinical information for diagnostics and designing novel therapeutic approaches for KS and nIHH in humans.
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 }}

Paolo E Forni其他文献

Paolo E Forni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('Paolo E Forni', 18)}}的其他基金

Understanding the role of the transcription factor Gli3 in Kallmann syndrome and normosmic forms of idiopathic hypogonadotropic hypogonadism.
了解转录因子 Gli3 在卡尔曼综合征和正常形式的特发性低促性腺激素性性腺功能减退症中的作用。
  • 批准号:
    10112936
  • 财政年份:
    2019
  • 资助金额:
    $ 44.99万
  • 项目类别:
Understanding the role of the transcription factor Gli3 in Kallmann syndrome and normosmic forms of idiopathic hypogonadotropic hypogonadism.
了解转录因子 Gli3 在卡尔曼综合征和正常形式的特发性低促性腺激素性性腺功能减退症中的作用。
  • 批准号:
    9892022
  • 财政年份:
    2019
  • 资助金额:
    $ 44.99万
  • 项目类别:
Understanding the role of the transcription factor Gli3 in Kallmann syndrome and normosmic forms of idiopathic hypogonadotropic hypogonadism.
了解转录因子 Gli3 在卡尔曼综合征和正常形式的特发性低促性腺激素性性腺功能减退症中的作用。
  • 批准号:
    10355446
  • 财政年份:
    2019
  • 资助金额:
    $ 44.99万
  • 项目类别:
Understanding the role of the transcription factor Gli3 in Kallmann syndrome and normosmic forms of idiopathic hypogonadotropic hypogonadism.
了解转录因子 Gli3 在卡尔曼综合征和正常形式的特发性低促性腺激素性性腺功能减退症中的作用。
  • 批准号:
    10570176
  • 财政年份:
    2019
  • 资助金额:
    $ 44.99万
  • 项目类别:
Molecular Mechanisms Controlling Differentiation and Circuit Formation of Vomeronasal Sensory Neurons
控制犁鼻感觉神经元分化和回路形成的分子机制
  • 批准号:
    10292450
  • 财政年份:
    2018
  • 资助金额:
    $ 44.99万
  • 项目类别:
Molecular Mechanisms Controlling Differentiation and Circuit Formation of Vomeronasal Sensory Neurons
控制犁鼻感觉神经元分化和回路形成的分子机制
  • 批准号:
    10532370
  • 财政年份:
    2018
  • 资助金额:
    $ 44.99万
  • 项目类别:
Molecular Mechanisms Controlling Differentiation and Circuit Formation of Vomeronasal Sensory Neurons
控制犁鼻感觉神经元分化和回路形成的分子机制
  • 批准号:
    10049241
  • 财政年份:
    2018
  • 资助金额:
    $ 44.99万
  • 项目类别:

相似海外基金

How Spinal Afferent Neurons Control Appetite and Thirst
脊髓传入神经元如何控制食欲和口渴
  • 批准号:
    DP220100070
  • 财政年份:
    2023
  • 资助金额:
    $ 44.99万
  • 项目类别:
    Discovery Projects
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
  • 批准号:
    23K05594
  • 财政年份:
    2023
  • 资助金额:
    $ 44.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10477437
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
  • 批准号:
    10315571
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10680037
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10654779
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10275133
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
  • 批准号:
    10470747
  • 财政年份:
    2021
  • 资助金额:
    $ 44.99万
  • 项目类别:
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
  • 批准号:
    RGPIN-2014-05517
  • 财政年份:
    2018
  • 资助金额:
    $ 44.99万
  • 项目类别:
    Discovery Grants Program - Individual
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
  • 批准号:
    RGPIN-2014-05517
  • 财政年份:
    2017
  • 资助金额:
    $ 44.99万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了