Signal Integration During Eye Formation

眼睛形成过程中的信号整合

• 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
• 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

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: