CAREER: Contact inhibition of locomotion as a positioning mechanism during endoderm morphogenesis
职业:运动的接触抑制作为内胚层形态发生过程中的定位机制
基本信息
- 批准号:2238304
- 负责人:
- 金额:$ 100万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-12-15 至 2027-11-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
In multicellular organisms, tissues, organs, and even the entire body plan are built through the actions of many individual cells. Understanding how cells coordinate their actions with each other remains an outstanding question in biology. This study will use zebrafish embryos to understand how a population of embryonic cells called endodermal cells work together to build a tissue that will eventually become parts of the gastrointestinal and respiratory systems. In humans, endoderm malformations affect an estimated 10 per 10,000 births. Zebrafish embryos will be used in this study because they are transparent and develop externally (outside the mother), making it easy to image cellular interactions within a living, intact organism. Preliminary work suggested that, counterintuitively, zebrafish endodermal cells disperse apart before coming back together to form a tissue. This study aims to understand how and why endodermal cells undergo these two very different behaviors (dispersal and convergence) during tissue formation. This research will be integrated with an education and outreach program designed to expand access to authentic research experiences and enhance STEM education for undergraduate students and the general public. This education and outreach program consists of: 1) a course-based undergraduate research experience (CURE) for students enrolled at the University of California, Merced, 2) a summer program that will give undergraduate students direct experience working on an independent project in a research lab, and 3) an educational exhibit on developmental biology and microscopy for a local children’s’ museum designed in partnership with teachers-in-training.The endoderm is one of the three primary germ layers that gives rise to the gut and respiratory epithelia and other organs. However, endodermal cells are highly migratory during gastrulation and before differentiating into mature epithelia. This study will take advantage of the zebrafish embryo’s amenability for in vivo imaging to characterize the continuum of cellular behaviors that occur as cells differentiate from migratory endodermal precursors into epithelial cells. During gastrulation stages, zebrafish endodermal cells first disperse away from each other before eventually converging into a coherent epithelial sheet. Preliminary studies suggested that endodermal cells initially avoid each other through contact-triggered inhibition of locomotion. This study will determine the molecular mechanisms driving these inhibitory interactions and their significance to tissue formation. Aim 1 will identify the cell surface receptors that allow endodermal cells to recognize and repel away from each other. Aim 2 will define the intracellular signaling pathways that regulate inhibitory responses and the initial dispersal of endodermal cells. Aim 3 will determine how these inhibitory interactions are modulated as cells switch from dispersal to convergence movements. This study will demonstrate how transient, hyperlocal cell-cell interactions can lead to large-scale patterning, with broad implications for tissue morphogenesis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
在多细胞生物体中,组织、器官甚至整个身体都是通过许多单个细胞的作用建立起来的。了解细胞如何相互协调它们的行动仍然是生物学中一个悬而未决的问题。这项研究将使用斑马鱼胚胎来了解一群称为内胚层细胞的胚胎细胞如何共同构建一个最终成为胃肠道和呼吸系统的组织。在人类中,估计每10,000名新生儿中就有10人受到内胚层畸形的影响。斑马鱼胚胎将被用于这项研究,因为它们是透明的,并且在外部(在母体之外)发育,这使得在一个完整的生物体中成像细胞相互作用变得容易。初步工作表明,与直觉相反,斑马鱼内胚层细胞在重新聚集在一起形成组织之前会分散开来。本研究旨在了解内胚层细胞在组织形成过程中如何以及为什么会经历这两种非常不同的行为(分散和聚集)。这项研究将与教育和推广计划相结合,旨在扩大获得真实研究经验的机会,并加强本科生和公众的STEM教育。该教育和推广计划包括:1)为加州大学默塞德分校入学的学生提供基于课程的本科研究体验(CURE),2)暑期课程,将为本科生提供在研究实验室从事独立项目的直接经验,及3)为一间儿童博物馆举办有关发育生物学及显微镜的教育展览,内胚层是产生肠道和呼吸上皮细胞以及其他器官的三个主要胚层之一。然而,内胚层细胞在原肠胚形成期间和分化成成熟上皮细胞之前是高度迁移的。这项研究将利用斑马鱼胚胎的顺从性在体内成像的特点,发生细胞从迁移的内胚层前体分化成上皮细胞的细胞行为的连续性。在原肠胚形成阶段,斑马鱼内胚层细胞首先分散远离彼此,然后最终汇聚成一个连贯的上皮片。初步研究表明,内胚层细胞最初通过接触触发的运动抑制来避免彼此。本研究将确定驱动这些抑制性相互作用的分子机制及其对组织形成的意义。目的1将确定允许内胚层细胞识别和排斥彼此的细胞表面受体。目的2将定义调节抑制反应和内胚层细胞初始分散的细胞内信号通路。目标3将确定当细胞从分散运动切换到会聚运动时,这些抑制性相互作用是如何被调制的。这项研究将展示如何短暂的,超局部细胞间的相互作用可以导致大规模的图案,与广泛的影响组织morphogenesis.This奖项反映了NSF的法定使命,并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。
项目成果
期刊论文数量(0)
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Stephanie Woo其他文献
Sa1523 EXPLORING FACTORS FOR IMPROVED DIAGNOSIS OF CHOLEDOCHAL CYSTS USING ERCP
- DOI:
10.1016/s0016-5085(24)01552-x - 发表时间:
2024-05-18 - 期刊:
- 影响因子:
- 作者:
Angela Troia;Srikar Reddy;Ann F. Kopera;Lynette Sequeira;Carolyn Hofley;Emily R. Winslow;Nadim Haddad;Walid Chalhoub;Stephanie Woo;Mark Real - 通讯作者:
Mark Real
Su1124 DETECTION OF PRECANCEROUS COLONIC POLYPS IN PATIENTS AGED 40-49: AN ANALYTICAL STUDY
- DOI:
10.1016/s0016-5085(24)01979-6 - 发表时间:
2024-05-18 - 期刊:
- 影响因子:
- 作者:
Ade Waterman;Ahmad Abdulraheem;Ghaith Almhanni;Fan Cao;Anuja Shah;Stephanie Woo;Priyanka Kanth - 通讯作者:
Priyanka Kanth
Fr421 UNEMPLOYMENT ASSOCIATED WITH HIGHER RISK OF POST-TRANSPLANT ALCOHOL RECIDIVISM
- DOI:
10.1016/s0016-5085(21)02676-7 - 发表时间:
2021-05-01 - 期刊:
- 影响因子:
- 作者:
Stephanie Woo;Zaeema Zafar;Christine Hsu;Amol Rangnekar - 通讯作者:
Amol Rangnekar
Sa1133: APC VERSUS AMPULLECTOMY IN THE MANAGEMENT OF PANCREATIC AMPULLARY ADENOMAS
- DOI:
10.1016/s0016-5085(22)60760-1 - 发表时间:
2022-05-01 - 期刊:
- 影响因子:
- 作者:
Palak Patel;Stephanie Woo;Walid Chalhoub - 通讯作者:
Walid Chalhoub
Mo1585 EXTENDED POST-LIVER TRANSPLANT OPIOID USE ASSOCIATED WITH EARLY ALCOHOL RECIDIVISM
- DOI:
10.1016/s0016-5085(23)04219-1 - 发表时间:
2023-05-01 - 期刊:
- 影响因子:
- 作者:
Daniel T. Gildea;Stephanie Woo;Krystina A. Johnson-Laghi;Christine Hsu;Amol Rangnekar - 通讯作者:
Amol Rangnekar
Stephanie Woo的其他文献
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