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.

体内每个器官在发育过程中都采用特定形状，并假设正确 形状对于器官功能至关重要。这里提出的研究研究了这个复杂的过程 使用脊椎动物眼作为模型系统。建立适当的形状 发育对于眼睛的功能至关重要，并且在变化中引起的发育偏差 形式导致人类和视觉障碍的结构性眼部缺陷。而许多基因 这些缺陷的基础已被鉴定出来，对遗传变异的了解少得多 导致导致这些结构缺陷的细胞行为变化。该建议使用 墨西哥盲人山cave鱼阿斯蒂亚纳克斯墨西哥us作为模型系统，以检查遗传和 眼睛形态发生中天然偏差的细胞基础。答：墨西哥存在两者 形式，瞄准的，居住的形式和一种盲目的洞穴居住形式，最初发展很小 随后退化的眼睛。山洞的眼睛在形状上显示出差异 与表面鱼相比，开发允许检查细胞机制 这是这些差异的基础。此外，洞穴大脑与表面鱼有显着不同 大脑，提供了一个机会，可以调查发育中的眼睛与 发育中的大脑。眼睛如何假定其正确的形状，这如何影响 大脑以及在细胞水平上自然遗传变异对这些过程的影响将是 利用基因编辑和转基因技术检查，结合现场成像和 建立的大脑图集。此外，因为眼睛形成的过程是高度保守的 在物种之间，这些研究可能会进一步了解结构性眼缺陷 人类发生。