Development and Patterning of the Enteric Nervous System
Development and Patterning of the Enteric Nervous System
批准号:
10741619
负责人:
Julia Anna Kaltschmidt
金额:
$43.13万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-01 至 2025-07-31
关键词:
AffectAgeAnatomyArchitectureBirthCalciumCentral Nervous SystemCharacteristicsChildChildhoodCongenital MegacolonDataDefectDeoxyuridineDevelopmentDevelopmental BiologyDigestive System DisordersDistalEmbryoEnteralEnteric Nervous SystemFailureFelis catusFunctional disorderGastrointestinal DiseasesGastrointestinal MotilityGenesGoalsImageImmunohistochemistryIntestinal Pseudo-ObstructionIntestinesKnowledgeLengthLinkLocationMapsMissionMolecularMonitorMusMutant Strains MiceMutationNervous SystemNervous System PhysiologyNervous System controlNeural CrestNeuronsOutcomePatternPeriodicityPopulationPremature InfantProcessProteinsQuality of lifeRoleSignal TransductionSmooth MuscleStructureStructure-Activity RelationshipTestingTissuesUnited States National Institutes of HealthVisualWorkcell motilitycell typeexperimental studygastrointestinalgastrointestinal functionhuman diseaseimprovedinfancyinsightmelanocytemortalitymotility disordermouse modelneonatal micenervous system developmentneural networknovelpediatric patientsperinatal periodpostnatalprematurespatiotemporal
中文摘要
项目摘要
在早产或胃肠动力的背景下,胃肠(GI)动力发作失败
疾病,是儿科人群神经发育迟缓和死亡的重要原因。的
肠神经系统(ENS),肠壁内的局部神经系统,是肠神经系统的主要驱动力。
胃肠道动力。我们最近已经证明,肠神经元组织成一个宏观结构,
周向取向的条纹,这是由于肠神经元从随机的
排列成神经条。这种模式的功能意义尚不清楚,但胃肠道运动,
直到神经元条纹已经建立的时间点才出现。此外,ENS结构的破坏,
如发生在人类疾病如先天性巨结肠和某些小鼠模型中,
功能障碍在这里,我们建议描述这种明显的结构-功能关系的发展
我们将进一步研究模式化基因Taqpep在胚胎和新生小鼠ENS中的作用,
ENS模式和GI功能。Taqpep先前已被证明可以调节条纹猫的皮毛图案,
我们的初步数据表明Taqpep也影响肠神经元条纹的周期性。建立
ENS发育过程中结构和功能之间的关系,我们将绘制GI运动,神经元
多样性和神经网络功能的逐步条纹图案的发展ENS(目的1)。在
此外,我们将研究ENS模式和胃肠道运动在Taqpep突变小鼠,以确定如何微妙
ENS模式的改变影响GI功能(目的2)。总的来说,这个项目将描述
ENS结构和胃肠道运动之间的联系,并揭示控制ENS模式的分子机制
和胃肠道蠕动这种对ENS结构和功能的新理解将产生对ENS的关键基本见解
发展和提供新的途径来询问胃肠道不成熟的病理生理和治疗,
小儿胃肠动力障碍。
英文摘要
Project Summary
Failure in the onset of gastrointestinal (GI) motility, either in the context of prematurity or GI motility
disorders, is a significant cause of neurodevelopmental delay and mortality in the pediatric population. The
enteric nervous system (ENS), the local nervous system within the walls of the intestine, is the primary driver of
GI motility. We have recently demonstrated that enteric neurons are organized into a macrostructure of
circumferentially oriented stripes, which arise from progressive reorganization of enteric neurons from a random
array into neuronal stripes. The functional significance of this patterning is not understood, yet GI motility does
not arise until a timepoint when neuronal stripes have been established. Further, disruptions to ENS structure,
as occur in human diseases like Hirschsprung’s disease and in certain mouse models, are associated with GI
dysfunction. Here, we propose to characterize the development of this apparent structure-function relationship
in the embryonic and neonatal mouse ENS. We will further investigate the role of the patterning gene Taqpep in
ENS patterning and GI function. Taqpep has previously been shown to modulate striped cat coat patterning, and
our preliminary data suggest that Taqpep also influences the periodicity of enteric neuronal stripes. To establish
a relationship between structure and function during ENS development, we will map GI motility, neuronal
diversity, and neural network function onto the progressive striped patterning of the developing ENS (Aim 1). In
addition, we will investigate ENS patterning and GI motility in Taqpep mutant mice to determine how subtle
alterations to ENS patterning affect GI function (Aim 2). Overall, this project will characterize the relationship
between ENS structure and GI motility as well as uncover a molecular mechanism that controls ENS patterning
and GI motility. This novel understanding of ENS structure and function will yield critical basic insights into ENS
development and provide new avenues to interrogate the pathophysiology and treatment of GI immaturity and
pediatric GI motility disorders.
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会议论文
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:9521466
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资助金额:$37.08万
-
财政年份:2017
-
负责人:Julia Anna Kaltschmidt
-
依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:8692038
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资助金额:$36.04万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:8868192
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项目类别:
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资助金额:$36.63万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:10413154
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项目类别:
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资助金额:$36.26万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:8562065
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项目类别:
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资助金额:$36.19万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:9093872
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项目类别:
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资助金额:$36.85万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:10159975
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项目类别:
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资助金额:$36.36万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
Molecular Mechanisms Regulating Inhibitory Circuitry in the Spinal Cord
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批准号:10624944
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项目类别:
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资助金额:$36.16万
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财政年份:2013
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负责人:Julia Anna Kaltschmidt
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依托单位:
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