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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?

项目总结: