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Development of Zebrafish Enteric Nervous System and Intestinal Smooth Muscle

斑马鱼肠神经系统和肠平滑肌的发育

基本信息

批准号：
7195477
负责人：
KENNETH N WALLACE
金额：
$ 23.85万
依托单位：
CLARKSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-11 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7195477
关键词：
Address Animal Model Anterior Appearance Axon BMP4 Biological Models Birds Chickens Class Colon Congenital Megacolon Data Defect Development Development, Other Digestive System Disorders Disease Early identification Embryo Embryonic Development Enteral Enteric Nervous System Event Experimental Designs FK506 Future Gastrointestinal tract structure Genes Genetic Genus Cola Homeostasis Homologous Gene Human Immigration Intestines Investigation Lateral Lead Length Live Birth Mesenchyme Methods Modeling Molecular Molecular Abnormality Motor Movement Mus Muscle Development Nature Neural Crest Cell Neural tube Neuroglia Neuronal Differentiation Neurons Numbers Organ Pathway interactions Pattern Personal Satisfaction Phenotype Placement Play Process Proliferating Protein Inhibition Rate Role Sensory Series Signal Pathway Signal Transduction Smooth Muscle Staging Stream Structure System Testing Time Transcript Vertebrates Zebrafish day gastrointestinal system in vivo information gathering inhibitor/antagonist migration mutant nerve supply neurodevelopment relating to nervous system research study

项目摘要

DESCRIPTION (provided by applicant): The enteric nervous system plays a critical role in normal function of the intestine. Enteric neurons provide motor and sensory information to generate propulsive movement and maintain organ homeostasis. Enteric neurons originate from neural crest cells, migrate to the rostral portion of the digestive system, enter the outer mesenchyme, and migrate to the caudal end. Along the way, the enteric precursors proliferate and differentiate into neurons and glia thereby innervating the entire organ. The critical nature of enteric neuron innervation of the intestine is demonstrated by Hirschsprung's disease. This digestive disease occurs in 1 in 5000 live births and results in aganglionic segments of the human colon. The length of aganglionic intestinal segments varies due to multiple genetic abnormalities that give rise to the disease. Genes responsible for development of the enteric neurons are strongly conserved across multiple vertebrate species, including zebrafish. Genetic conservation combined with conservation of structure and function of the vertebrate digestive system makes animal models like zebrafish an effective model to study the genetics of enteric and smooth muscle development. We will use zebrafish to determine additional genetic components underlying migration and differentiation of enteric precursors and development of smooth muscle. Previous investigations have determined that enteric neurons develop using homologous pathways that have been identified in other model systems. Specific aim1 will identify the wild type pattern of enteric proliferation and neuronal subtype differentiation. Specific aim 2 tests the hypothesis that the zebrafish homologue of zFKBP/SMAP and BMP signaling are critical for development of enteric and intestinal smooth muscle. Specific aim 3 tests the hypothesis that the enteric and intestinal smooth muscle defects in digestive mutants flotte latte(flo) and slimjim (slj) are due in part to identified homologous signaling pathways. These experiments will lead to a more complete understanding of the genetics of enteric and smooth muscle development and the components that underlie Hirschprung's disease.

描述（由申请人提供）：肠神经系统在肠的正常功能中起关键作用。肠神经元提供运动和感觉信息，以产生推进运动和维持器官内稳态。肠神经元起源于神经嵴细胞，迁移到消化系统的吻侧部分，进入外间充质，并迁移到尾端。沿着，肠前体增殖并分化成神经元和神经胶质，从而支配整个器官。先天性巨结肠病证明了肠神经元支配肠道的重要性。这种消化系统疾病的发生率为1/5000活产，并导致人类结肠的无神经节段。无神经节肠段的长度因引起疾病的多种遗传异常而变化。负责肠神经元发育的基因在包括斑马鱼在内的多种脊椎动物物种中高度保守。遗传保守性与脊椎动物消化系统结构和功能的保守性相结合，使得斑马鱼等动物模型成为研究肠道和平滑肌发育遗传学的有效模型。我们将使用斑马鱼，以确定其他遗传成分的迁移和分化的肠道前体和平滑肌的发展。以前的研究已经确定，肠神经元的发展使用同源途径，已确定在其他模型系统。特异性aim 1将鉴定肠增殖和神经元亚型分化的野生型模式。具体目的2测试zFKBP/SMAP和BMP信号传导的斑马鱼同源物对于肠和肠平滑肌的发育至关重要的假设。具体目标3测试的假设，即肠道和肠平滑肌缺陷的消化突变体flotte latte（flo）和slimjim（slj）是由于部分确定同源信号通路。这些实验将导致更全面地了解肠道和平滑肌发育的遗传学以及导致先天性巨结肠症的组成部分。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish.

DOI：
10.1021/es9010543
发表时间：
2009-08-15
期刊：
ENVIRONMENTAL SCIENCE & TECHNOLOGY
影响因子：
11.4
作者：
Ispas, Cristina;Andreescu, Daniel;Patel, Avni;Goia, Dan V.;Andreescu, Silvana;Wallace, Kenneth N.
通讯作者：
Wallace, Kenneth N.

Electrochemical quantification of serotonin in the live embryonic zebrafish intestine.