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小分裂球独特的代谢调控有助于海胆胚胎的原肠胚形成。

Unique metabolic regulation of micromeres contributes to gastrulation in the sea urchin embryo.

作者信息

Isaac Shakson, Dubosky Douglas, Waldron Ashley, Emura Natsuko, Furze Aidan, Rao Kavya, Mori Masaru, Ragavendran Ashok, Makinoshima Hideki, Yajima Mamiko

机构信息

Department of Molecular Biology, Cell Biology & Biochemistry, Brown University, Providence, RI, USA.

Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.

出版信息

Nat Commun. 2025 Aug 11;16(1):7410. doi: 10.1038/s41467-025-62697-8.

Abstract

During development, a group of cells called organizers plays critical roles by sending signals to adjacent cells and controlling embryonic and tissue patterning. Recent studies suggest that these inductive cells facilitate the downstream signaling pathways conserved across organisms. However, what makes these cells fundamentally inductive is little understood. In this study, we demonstrate that the micromeres of the sea urchin, one of the known organizers, have distinct metabolic properties compared to the rest of the embryo. The specific metabolic inhibitors for sugar metabolism (2-DG), fatty acid synthesis (cerulenin), and N-linked glycosylation (tunicamycin) compromise micromeres' regulatory capacity, altering the downstream germ layer patterning in the resultant embryos. Notably, the endoplasmic reticulum (ER) asymmetrically localizes during asymmetric cell division, resulting in the enrichment of ER and Wnt protein at the vegetal cortex of micromeres. Metabolic inhibition appears to compromise ER activity in Wnt particle distribution. We propose that the micromere ER is sensitive to specific metabolic regulation, contributing to the inductive signaling activity. This study provides a paradigm of how ER and metabolic regulation contribute to the inductive capability of the cells.

摘要

在发育过程中,一群被称为组织者的细胞通过向相邻细胞发送信号并控制胚胎和组织模式形成发挥着关键作用。最近的研究表明,这些诱导细胞促进了生物体间保守的下游信号通路。然而,这些细胞从根本上具有诱导性的原因却鲜为人知。在本研究中,我们证明海胆的小分裂球(已知的组织者之一)与胚胎的其他部分相比具有独特的代谢特性。糖代谢(2-脱氧葡萄糖)、脂肪酸合成(浅蓝菌素)和N-连接糖基化(衣霉素)的特异性代谢抑制剂损害了小分裂球的调节能力,改变了所得胚胎中下游胚层的模式形成。值得注意的是,内质网(ER)在不对称细胞分裂过程中不对称定位,导致ER和Wnt蛋白在小分裂球的植物皮质富集。代谢抑制似乎会损害Wnt颗粒分布中的ER活性。我们提出,小分裂球内质网对特定的代谢调节敏感,这有助于诱导信号活性。这项研究提供了一个内质网和代谢调节如何促进细胞诱导能力的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ba4/12340151/5a7c70833c2c/41467_2025_62697_Fig1_HTML.jpg

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