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囊性纤维化跨膜电导调节因子(CFTR)在斑马鱼早期胚胎发生过程中调节胚胎组织者的形成。

Cystic fibrosis transmembrane conductance regulator (CFTR) regulates embryonic organizer formation during zebrafish early embryogenesis.

机构信息

1Prenatal Diagnosis Center, Department of Obstetrics and Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.

出版信息

Int J Dev Biol. 2020;64(7-8-9):409-413. doi: 10.1387/ijdb.190373hs.

Abstract

Cystic fibrosis (CF) is associated with the manifestation of a number of medical conditions throughout the body. This prompted us to investigate the etiology of CF from the viewpoint of the embryonic organizer, which is responsible for steering the movement of surrounding cells into specific organs and tissues. In our previous work, we found that a cftr mutant had decreased nuclear β-catenin levels in the early embryo at 5 hours post-fertilization (hpf), when the organizer forms. It is known that nuclear β-catenin signaling is essential for the induction of the dorsal organizer. Therefore, we explored the role of cftr in the formation of the embryonic organizer in this work. Indeed, the expression of organizer and germ layer markers was significantly affected in cftr mutant embryos dependent on Wnt/β-catenin signaling. Furthermore, quantitative proteome analysis revealed that the cftr mutant induced significant alteration in the expression of proteins related to many critical biological processes, cellular components, molecular functions, and signaling pathways, except for the Wnt/β-catenin pathway. These findings demonstrate the function of cftr in embryonic organizer formation and provide an explanation for why many abnormalities occur in the bodies of CF patients.

摘要

囊性纤维化 (CF) 与全身多种医疗状况的表现有关。这促使我们从胚胎组织者的角度研究 CF 的病因,胚胎组织者负责引导周围细胞向特定器官和组织移动。在我们之前的工作中,我们发现 cftr 突变体在受精后 5 小时(hpf)早期胚胎中核 β-catenin 水平降低,此时组织者形成。已知核 β-catenin 信号对于背侧组织者的诱导至关重要。因此,我们在这项工作中探索了 cftr 在胚胎组织者形成中的作用。事实上,cftr 突变体胚胎中组织者和胚层标记物的表达显著受 Wnt/β-catenin 信号的影响。此外,定量蛋白质组分析表明,cftr 突变体诱导与许多关键生物学过程、细胞成分、分子功能和信号通路相关的蛋白质表达发生显著改变,除了 Wnt/β-catenin 通路。这些发现表明 cftr 在胚胎组织者形成中的作用,并解释了为什么 CF 患者的身体会出现许多异常。

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