Signal Integration During Eye Formation

眼睛形成过程中的信号整合

基本信息

批准号：
10666489
负责人：
Nadean L Brown
金额：
$ 39.25万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
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：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10666489
关键词：
Alleles Anophthalmos Apoptosis Binding Bioinformatics Biology Brain Cancer Biology Cell Maintenance Cell Polarity Cell Proliferation Cell membrane Cell surface Cells Cilia Coloboma Complex Confocal Microscopy Cre driver Data Development Diffusion Disease Early identification Embryo Embryology Enhancers Etiology Eye Eye Abnormalities Eye Development Generations Genes Genetic Goals Growth Histology Holoprosencephaly Hour Human Hypothalamic structure Immunohistochemistry Impairment In Situ Hybridization In Vitro Ligands Microphthalmos Molecular Morphogenesis National Eye Institute Neural Retina Neurons Optic Disk Optic Nerve Optic vesicle Organogenesis Organoids Outer Limiting Membrane Pathogenesis Pathway interactions Pattern Pituitary Gland Process Production Proliferating Regulation Reporting Research Retina Retinal Cone Retinal Ganglion Cells Role SHH gene SMO gene Septo-Optic Dysplasia Signal Pathway Signal Transduction Sonic Hedgehog Pathway Spinal Cord Subthalamic structure System Techniques Technology Testing Time Tissues Transgenic Mice Transgenic Organisms Untranslated RNA Visual base diencephalon experimental study eye formation gastrulation histogenesis in vivo induced pluripotent stem cell insight lens malformation morphogens mouse genetics mutant mutant mouse model neurogenesis notch protein optic cup optic stalk receptor receptor expression response retinal progenitor cell skin organogenesis smoothened signaling pathway spatiotemporal stem cell biology stem cells

项目摘要

Project Summary: A long-standing question in biology is how cells respond to multiple signaling inputs with a specific response. This proposal investigates the intersections of Notch and Hh signaling pathways, which are widely required during development, and basic mechanisms congenital eye disease. Both signaling systems regulate cell proliferation, morphogenesis, cell polarity, differentiation, apoptosis and stem cell maintenance. However, the spatiotemporal contexts for each differs at the cellular and tissue levels during optic vesicle morphogenesis and growth. This proposal will use in vivo complex conditional (cre-lox) mouse genetics, mouse transgenics, embryology, iPSC-derived retinal organoids, histology, immunohistochemistry, confocal microscopy, in situ hybridization, qPCR and bioinformatics technologies to investigate basic, mechanistic questions about the initiation and progression of eye formation from the embryonic brain. We will address several important questions: 1) What are the spatial and temporal constraints for Notch versus Hh in controlling growth, morphogenesis, patterning, tissue polarity and the timing of differentiation in the optic vesicle, optic cup, RPE and optic stalk? 3) What are the optimal conditions by which Notch and Shh pathways contribute to the generation of retinal ganglion cell and cone photoreceptor neurons in retinal organoid culture? 1) How do the Notch and Hh pathways regulate the eye expression domains of a common target gene, Hes1?

项目概要：生物学中一个长期存在的问题是细胞如何对多个信号输入做出特定反应。该提案研究了广泛需要的 Notch 和 Hh 信号通路的交叉点发育期间和先天性眼病的基本机制。这两种信号系统都调节细胞。然而，增殖、形态发生、细胞极性、分化、凋亡和干细胞维持。在视囊泡形态发生过程中，每个细胞和组织水平的时空背景都不同该提案将使用体内复杂条件（cre-lox）小鼠遗传学、小鼠转基因技术，胚胎学、iPSC 衍生的视网膜类器官、组织学、免疫组织化学、共聚焦显微镜、原位杂交、qPCR 和生物信息学技术来研究有关眼睛形成的起始和进展是从胚胎大脑开始的。我们将讨论几个重要的问题问题：1) Notch 与 Hh 在控制生长方面有哪些空间和时间限制，视泡、视杯、RPE 的形态发生、模式、组织极性和分化时间和视柄？ 3）Notch 和 Shh 通路有助于形成的最佳条件是什么？视网膜类器官培养中视网膜神经节细胞和视锥细胞感光神经元的生成 1) 如何进行？ Notch 和 Hh 通路调节共同目标基因 Hes1 的眼睛表达域？