MicroRNA regulation of neural tube closure

MicroRNA对神经管闭合的调节

基本信息

批准号：
10570194
负责人：
RICHARD H. FINNELL
金额：
$ 56.93万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-10 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10570194
关键词：
ATAC-seq Cell Nucleus Cells Chicken Model Chickens Chromatin Cilia Congenital Abnormality Critical Pathways Data Defect Development Diagnosis Disease Ectoderm Embryo Erinaceidae Evolution Expression Profiling Family Gene Expression Gene Silencing Genes Genetic Genetic Transcription Genomic DNA Goals Histologic Human In Situ In Vitro Infant Intervention Knock-out Knockout Mice Ligation Link Maps Messenger RNA MicroRNAs Molecular Mus Mutate Mutation Mutation Detection Neural Tube Closure Neural Tube Defects Neural Tube Development Neural tube Neuroepithelial Neuroepithelial Cells Nuclear Organoids Pathogenicity Pathway interactions Patients Phenotype Play Prevalence Process Public Health Regulation Regulatory Element Reporter Research Resolution Role SOX1 gene Sampling Structural Congenital Anomalies Structure System Testing Transcript Untranslated RNA Variant Wild Type Mouse Work cell type cohort embryonic stem cell exome sequencing experimental study folic acid supplementation gain of function genome sequencing human embryonic stem cell human model improved in vivo insight loss of function mouse model nerve stem cell neural neuroepithelium neuroregulation novel planar cell polarity pluripotency posttranscriptional prenatal prevent programs single cell analysis single-cell RNA sequencing smoothened signaling pathway transcriptome sequencing virtual whole genome

项目摘要

The goal of this project is to define the molecular mechanisms governing neural tube closure. Neural tube defects (NTDs) are amongst the most common human structural congenital malformations. In this project, we focus on a highly expressed microRNA family in pluripotency, miR-302, which plays a critical role during neural tube closure. Using genetic loss-of-function mouse, chicken and human models, we find that miR-302 is required to prevent precocious differentiation of the neuroepithelium. Additionally, we present data suggesting that miR- 302 is mutated in humans with neural tube closure defects. This project will provide insight into the earliest stages of neural tube development and inform our understanding of how microRNAs control this critical process.

该项目的目标是定义控制神经管闭合的分子机制。神经管缺陷（NTD）是最常见的人类结构性先天畸形之一。在这个项目中，我们重点关注多能性高表达的 microRNA 家族 miR-302，它在神经管闭合过程中发挥着关键作用。使用遗传功能丧失的小鼠、鸡和人类模型，我们发现 miR-302 是防止神经上皮过早分化所必需的。此外，我们提供的数据表明 miR-302 在患有神经管闭合缺陷的人类中发生突变。该项目将深入了解神经管发育的最早阶段，并让我们了解 microRNA 如何控制这一关键过程。