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Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration

整合成像和计算来表征心肌发育和再生中的神经嵴细胞

基本信息

批准号：
9806864
负责人：
Yichen Ding
金额：
$ 11.75万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-05 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9806864
关键词：
3-Dimensional Ablation Animal Genetics Animal Model Architecture Biology Blood Vessels Branchial arch structure Cardiac Cardiac Myocytes Cells Collaborations Consult Defect Development Developmental Biology Diastole Diphtheria Toxin Dominant-Negative Mutation Doxorubicin Embryo Fishes Fluorescence Microscopy Genetic Engineering Genetic Models Goals Health Sciences Heart Heart Abnormalities Heart Injuries Heterogeneity Image Joints Knowledge Light Literature Magnetic Resonance Imaging Mechanics Mediating Medical center Mentorship Messenger RNA Modeling Mus Myocardial Myocardium Natural regeneration Neonatal Neural Crest Neural Crest Cell Neural tube Notch Signaling Pathway Oregon Periodicals Phase Phenotype Physiological Population Recovery of Function Regulation Resolution Role Signal Transduction Stem cells Structure Systole Techniques Testing Tracer Transgenic Animals Transgenic Model Transgenic Organisms Universities Ventricular Ventricular Remodeling Zebrafish base congenital heart disorder fluorescence microscope heart dimension/size image processing improved insight mechanotransduction migration mouse model mutant neural network notch protein overexpression professor repaired restoration septal defect spatiotemporal virtual reality

项目摘要

Project Summary / Abstract Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration Cardiac neural crest cells are a population of highly migratory cells emerging from the neural tube, migrating through the pharyngeal arches and integrating into the developing heart. Recent advances demonstrate that a new sub-population of neural crest cells has the capacity to integrate into the cardiac chamber and differentiate into cardiomyocytes in both zebrafish and mice. Notch signaling regulates cardiomyocyte proliferation and differentiation during ventricular chamber development. Despite the knowledge gained in the past decades, the contribution of neural crest-derived cardiomyocytes to contractile function and the role of these cardiomyocytes in Notch signaling-mediated ventricular remodeling remain elusive. The small heart size in zebrafish embryos and neonatal mice also hinders precise cardiac structural and functional assessment. For these reasons, I seek to integrate our advanced imaging (sub-voxel resolution light-sheet fluorescence microscopy, SV-LSFM) with computation (displacement analysis of myocardial mechanical deformation, DIAMOND) to characterize the structural and functional contributions of the neural crest-derived cardiomyocytes to the myocardial development and regeneration with high spatiotemporal resolution. Under the joint mentorship from Professor Tzung Hsiai (Mechanotransduction, UCLA), Professor Jau-Nian Chen (Developmental biology, UCLA) and Professor Debiao Li (MR imaging, Cedars-Sinai Medical Center), I will continue to collaborate with Professor Atsushi Nakano (Developmental biology, UCLA) and Dr. Adam Langenbacher (Developmental biology, UCLA), and consult with Professor Joseph Wu (Cardiac stem cells, Stanford), Professor Sandra Rugonyi (Oregon Health & Science University), Professor Linda Demer (Vascular biology, UCLA) to test our hypothesis. We hypothesize that neural crest cells contribute to the ventricular myocardium and neural crest-derived cardiomyocytes are essential for the contractile function and ventricular repair. To test this hypothesis, we will have three aims. In Aim 1, we will elucidate the 4-D migration path of cardiac neural crest cell via SV-LSFM. In Aim 2, we will demonstrate 4-D structure and function following cardiac neural crest cell contribution to the ventricular myocardium via DIAMOND. In Aim 3, I will independently quantify the ventricular repair following the ablation of neural crest-derived cardiomyocytes in zebrafish and mouse models with my collaborators. In this context, we believe that the integration of genetic models with advanced imaging and computation will provide new mechanical and developmental insights into the contribution of neural crest cells to contractile function and ventricular repair under the regulation of Notch signaling pathway.

项目摘要/摘要