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Signal Integration During Eye Formation

眼睛形成过程中的信号整合

基本信息

批准号：
10245151
负责人：
Nadean L Brown
金额：
$ 34.27万
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/10245151
关键词：
Address 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 Diffuse Disease 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 Regulation Reporting Research Retina Retinal Cone Retinal Ganglion Cells Role 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 cell growth 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?

项目摘要：报告 -- 生物学研究中一个长期存在的问题是，细胞如何应对多个细胞信号输入以及特定的细胞反应。这项提案还调查了Notch路和HH路的两个交叉口，这些都是广泛需要的。在细胞发育过程中，细胞和细胞的基本调节机制是先天性眼球疾病。这两个信号系统都调节细胞周期。增殖、形态发生、细胞分化、细胞分化、细胞凋亡和干细胞的维持。然而，这是最重要的。在视神经小泡形态发生过程中，不同细胞和组织水平的时空环境是不同的。以及生长。这项新的提案将不再使用体内复杂的有条件基因(cre-lox)来研究小鼠的遗传，以及小鼠的转基因。胚胎学，IPSC衍生的视网膜组织学，组织学，免疫组织化学，激光共聚焦显微镜，原位观察。杂交、DNA定量聚合酶链式反应和现代生物信息学等技术需要更多地调查有关基因的基本、机械性的问题。眼睛形成的起始和进展过程始于胚胎的大脑。我们将主要讨论几个重要的问题。问题：*1)在控制经济增长方面，Notch和HH在空间和时间上的限制是什么？形态发生、图案化、组织分化、极性分化等是视网膜小泡、视神经杯、视网膜色素上皮细胞分化的主要时机。以及光学柄？-。视网膜神经节细胞的代谢率和视锥细胞感受器的代谢率在视网膜神经节细胞培养中的作用如何？ Noch基因和HH信号通路调节一个常见的靶向基因Hes1的眼睛和表达区域？