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.

身体中的每个器官在发育过程中都会呈现出特定的形状，并呈现出正确的 形状对器官功能至关重要。这里提出的研究考察了这一复杂的过程。 使用脊椎动物的眼睛作为模型系统。在此过程中建立适当的形状 发育对眼睛的功能至关重要，而导致变化的发育偏差 形体缺陷会导致人类的结构性眼睛缺陷和视觉障碍。虽然许多基因 这些缺陷的根本原因已经被识别出来，关于基因变异是如何产生的更少人知道 会导致细胞行为的改变，从而导致这些结构缺陷。本提案使用 以盲目墨西哥穴居鱼Astianax micianus为模型系统，研究其遗传和 自然发生的眼睛形态发生偏差的细胞基础。墨西哥黄蜂存在于两种环境中 形式，一种有视力的，表面居住的形式，和一种盲人的，洞穴居住的形式，最初发展成小的 眼睛随后退化。洞鱼的眼睛表现出不同的形状 与表层鱼类的发育相比，允许检查细胞机制 这是这些差异的基础。此外，穴居鱼的大脑与表层鱼有很大的不同 大脑，提供了一个机会来研究发育中的眼睛和 发育中的大脑。眼睛如何呈现其正确的形状，这如何影响眼睛的结构 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，结合现场成像和 已建立的脑图谱。此外，因为眼睛形态发生的过程是高度保守的 在物种之间，这些研究可能会进一步加深我们对结构性眼睛缺陷是如何在 人类会发生。