Gdf11 regulates left-right asymmetry development through TGF-β signal.

IF 5.9 1区生物学 Q2 CELL BIOLOGY

Cell Proliferation Pub Date : 2024-10-15 DOI:10.1111/cpr.13765

Wantao Yao, Zhaohui Wei, Xinning Tian, Jin Tan, Jingwen Liu

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Abstract

During the embryonic developmental stage in vertebrates, internal organs are arranged along the left-right axis. Disruptions in this process can result in congenital diseases or laterality disorders. The molecular mechanisms of left-right asymmetry in vertebrate development remain largely unclear. Due to its straightforward structure, zebrafish has become a favoured model for studying early laterality events. Here, we demonstrate that growth and development factor 11 (Gdf11) is essential for left-right development via TGF-β signalling. Morphological analysis showed that gdf11 morphants and mutants displayed clear heart and liver laterality disorders in a Nodal signal-dependent manner. Additionally, we found that Kupffer's vesicle formation and ciliogenesis were impaired following gdf11 deletion. We also observed that Gdf11 may form a heterodimer with Spaw, which promotes Smad2/3 phosphorylation and activates TGF-β signalling. Subsequently, Gdf11 promotes left-right laterality by stimulating Foxj1a and its target gene expression. In summary, we reveal a critical role of Gdf11 in left-right patterning, providing fundamental insights into the developmental process of left-right asymmetry.

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Gdf11通过TGF-β信号调节左右不对称发育

在脊椎动物的胚胎发育阶段，内脏器官沿左右轴排列。这一过程的中断会导致先天性疾病或侧位紊乱。脊椎动物发育过程中左右不对称的分子机制在很大程度上仍不清楚。由于结构简单，斑马鱼已成为研究早期侧向事件的理想模型。在这里，我们证明生长与发育因子 11（Gdf11）通过 TGF-β 信号对左右发育至关重要。形态学分析表明，生长与发育因子11变形体和突变体以依赖Nodal信号的方式表现出明显的心脏和肝脏侧位紊乱。此外，我们还发现 gdf11 基因缺失后，Kupffer 的囊泡形成和纤毛的生成也受到了影响。我们还观察到，Gdf11可能与Spaw形成异源二聚体，后者可促进Smad2/3磷酸化并激活TGF-β信号。随后，Gdf11通过刺激Foxj1a及其靶基因的表达来促进左右侧位。总之，我们揭示了 Gdf11 在左右模式化中的关键作用，为了解左右不对称的发育过程提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Proliferation 生物-细胞生物学

CiteScore

14.80

自引率

2.40%

发文量

198

审稿时长

1 months

期刊介绍： Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.