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: 10515241
• 负责人: Johanna E. Kowalko
• 金额: $ 37.53万
• 依托单位: LEHIGH 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515241
• 关键词: relationship; between; eye; morphogenesis; brain

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 形状对于器官功能至关重要。这里提出的研究检验了这个复杂的过程 使用脊椎动物的眼睛作为模型系统。期间建立适当的形状 发育对于眼睛的功能至关重要，而发育偏差会导致变化 形状会导致人类眼睛结构缺陷和视力障碍。虽然许多基因 这些缺陷的根源已被识别，但关于遗传变异如何发生却知之甚少。 导致细胞行为发生变化，从而导致这些结构缺陷。本提案使用 墨西哥盲穴鱼 Astyanax mexicanus 作为模型系统来检查遗传和 眼睛形态发生自然发生偏差的细胞基础。 A. mexicanus 存在两种 形态，一种有视力的、居住在地表的形态，以及一种盲目的、居住在洞穴中的形态，最初发育得很小 随后退化的眼睛。洞穴鱼的眼睛在生长过程中表现出不同的形状 与表面鱼类相比的发育，允许检查细胞机制 这些差异背后的原因。此外，洞穴鱼的大脑与表层鱼类显着不同 大脑，提供了一个机会来研究发育中的眼睛和 正在发育的大脑。眼睛如何呈现其正确的形状，这如何影响眼睛的结构 大脑，以及自然遗传变异在细胞水平上对这些过程的影响将是 利用基因编辑和转基因技术结合实时成像和 建立脑图谱。此外，由于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我们了解结构性眼睛缺陷如何影响 人类发生。

项目成果

A chromosome-level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution.

• DOI: 10.1038/s41467-021-21733-z
• 发表时间: 2021-03-04
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Warren WC;Boggs TE;Borowsky R;Carlson BM;Ferrufino E;Gross JB;Hillier L;Hu Z;Keene AC;Kenzior A;Kowalko JE;Tomlinson C;Kremitzki M;Lemieux ME;Graves-Lindsay T;McGaugh SE;Miller JT;Mommersteeg MTM;Moran RL;Peuß R;Rice ES;Riddle MR;Sifuentes-Romero I;Stanhope BA;Tabin CJ;Thakur S;Yamamoto Y;Rohner N
• 通讯作者: Rohner N