The relationship between eye morphogenesis and brain development

眼睛形态发生与大脑发育的关系

• 批准号: 10046461
• 负责人: Johanna E. Kowalko
• 金额: $ 8.81万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-03 至 2021-08-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046461
• 关键词: Affect; Anophthalmos; Anterior; Atlases; Base of the Brain; Biological Models; Blindness; Brain; Brain region; Cell Death; Cell Proliferation; Cells; Clinical; Coloboma; Complex; Congenital Disorders; Cues; Data; Defect; Development; Disease; Event; Eye; Eye Development; Family; Fishes; Fresh Water; Gene Expression; Gene Transfer Techniques; Genes; Genetic; Genetic Variation; Health; Homeobox; Human; Hybrids; Hyperactive behavior; Image; Lead; Mexican; Microphthalmos; Morphogenesis; Morphology; Movement; Optic vesicle; Optics; Organ; Pathway interactions; Population; Process; Research; Retina; Role; SHH gene; Shapes; Signal Transduction; Specific qualifier value; Structural defect; Structure; Surface; Techniques; Telencephalon; Testing; Variant; Vertebrates; Vision; Visual Fields; Visual impairment; Zebrafish; blind; brain morphology; cell behavior; egg; eye formation; genetic variant; mutant; neural plate; optic cup; optical imaging; progenitor; smoothened signaling pathway; stem cells

Each organ in the body assumes a specific shape during development, and assuming the correct shape is critical for organ function. The research proposed here examines this complex process using the vertebrate eye as a model system. Establishment of an appropriate shape during development is critical to function of the eye, and developmental deviations that cause in changes in form result in structural eye defects in humans and visual impairments. While many genes that underlie these defects have been identified, much less is known about how genetic variation results in changes to cellular behaviors that lead to these structural defects. This proposal uses the blind Mexican cavefish Astyanax mexicanus as a model system to examine the genetic and cellular basis of naturally occurring deviations in eye morphogenesis. A. mexicanus exists in two forms, a sighted, surface-dwelling form and a blind, cave-dwelling form that initially develops small eyes that subsequently degenerate. Cavefish eyes display differences in shape during development compared to surface fish, allowing for the examination of the cellular mechanisms that underlie these differences. Further, cavefish brains are significantly different from surface fish brains, providing an opportunity to investigate the relationship between the developing eye and the developing brain. How the eye assumes its proper shape, how this affects the structure of the brain, and the impact of natural genetic variants, at a cellular level, on these processes will be examined utilizing gene editing and transgenesis techniques, combined with live-imaging and an established brain atlas. Further, because the process of eye morphogenesis is highly conserved between species, these studies may further our understanding how structural eye defects in humans occur.

身体的每一个器官在发育过程中都具有特定的形状，并且具有正确的形状