Pancreatic islets of Langerhans display characteristic spatial architecture of their endocrine cell types. This architecture is critical for cell-cell communication and coordinated hormone secretion. Islet architecture is disrupted in type-2 diabetes. Moreover, the generation of architecturally correct islets in vitro remains a challenge in regenerative approaches to type-1 diabetes. Although the characteristic islet architecture is well documented, the mechanisms controlling its formation remain obscure. Here, we report that correct endocrine cell type sorting and the formation of mature islet architecture require the expression of Roundabout (Robo) receptors in β cells. Mice with whole-body deletion of Robo1 and conditional deletion of Robo2 either in all endocrine cells or selectively in β cells show complete loss of endocrine cell type sorting, highlighting the importance of β cells as the primary organizer of islet architecture. Conditional deletion of Robo in mature β cells subsequent to islet formation results in a similar phenotype. Finally, we provide evidence to suggest that the loss of islet architecture in Robo KO mice is not due to β cell transdifferentiation, cell death or loss of β cell differentiation or maturation.

中文翻译：

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Langerhans胰岛中的内分泌细胞类型分选和成熟结构需要在β细胞中表达回旋处受体。

Langerhans的胰岛显示其内分泌细胞类型的特征性空间结构。这种结构对于细胞间通讯和协调的激素分泌至关重要。胰岛结构在2型糖尿病中被破坏。而且，在结构上正确的胰岛的体外产生仍然是1型糖尿病的再生方法中的挑战。尽管特征化的胰岛结构已得到充分证明，但控制其形成的机制仍然不清楚。在这里，我们报告正确的内分泌细胞类型分类和成熟的胰岛体系结构的形成需要在β细胞中表达回旋（Robo）受体。在所有内分泌细胞中或在β细胞中具有Robo1全身缺失和Robo2有条件缺失的小鼠表现出内分泌细胞类型分选的完全丧失，强调了β细胞作为胰岛结构的主要组织者的重要性。胰岛形成后，成熟β细胞中Robo的条件缺失导致相似​​的表型。最后，我们提供证据表明在Robo KO小鼠中胰岛结构的丧失不是由于β细胞转分化，细胞死亡或β细胞分化或成熟的丧失。