Islet architecture in adult mice is actively maintained by Robo2 expression in β cells.

Islet architecture in adult mice is actively maintained by Robo2 expression in β cells.
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成年小鼠的胰岛结构由 β 细胞中的 Robo2 表达积极维持。

DOI:
10.1016/j.ydbio.2023.11.003
复制
发表时间:
2024
影响因子:
2.7
通讯作者:
Blum,Barak
Blum,Barak
中科院分区:
生物学3区
文献类型:
--
作者:
Waters,BayleyJ;Birman,ZoeR;Wagner,MatthewR;Lemanski,Julia;Blum,Barak

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发育生物学的一个基本问题是,在发育过程中形成的组织结构是为生命而设置的,还是需要持续的维护信号,如果是,这些信号是什么。胰腺中的朗格汉斯胰岛可以作为一个优雅的模型组织来回答这些问题。胰岛具有非随机的空间结构,这对正常的葡萄糖稳态很重要。胰岛结构在胚胎发育过程中形成,其形态发生过程部分涉及β细胞中Roundabout (Robo)受体及其配体Slit在周围间质中的表达。胰岛结构是在发育过程中形成并在成年后保持被动状态,还是在一生中都需要积极维护,目前还不确定。在这里,我们有条件地删除了成年小鼠的drobo2in β细胞,并在两个月的追逐后观察了它们的胰岛结构。我们发现,在成人β细胞中删除Robo2会导致胰岛结构的显著丧失,而不会影响β细胞的身份、成熟或应激,这表明Robo2在积极维持成人胰岛结构中起作用。了解维持胰岛结构所需的因素,从而优化胰岛功能,对于开发未来的糖尿病治疗方法非常重要。
A fundamental question in developmental biology is whether tissue architectures formed during development are set for life, or require continuous maintenance signals, and if so, what are those signals. The islets of Langerhans in the pancreas can serve as an elegant model tissue to answer these questions. Islets have a non-random spatial architecture, which is important to proper glucose homeostasis. Islet architecture forms during embryonic development, in a morphogenesis process partially involving expression of Roundabout (Robo) receptors in β cells, and their ligand, Slit, in the surrounding mesenchyme. Whether islet architecture is set during development and remains passive in adulthood, or whether it requires active maintenance throughout life, has not been determined. Here we conditionally deletedRobo2in β cells of adult mice and observed their islet architecture following a two-month chase. We show that deletingRobo2in adult β cells causes significant loss of islet architecture without affecting β cell identity, maturation, or stress, indicating that Robo2 plays a role in actively maintaining adult islet architecture. Understanding the factors required to maintain islet architecture, and thus optimize islet function, is important for developing future diabetes therapies.
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