Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells

Scientific Reports
Melissa T AdamsBarak Blum

Abstract

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 maturat...Continue Reading

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Citations

Dec 7, 2018·Nature Communications·Andreia V PinhoIlse Rooman
Dec 7, 2018·Nature Communications·Sophie EscotFrancesca M Spagnoli
Jun 6, 2020·Diabetes/metabolism Research and Reviews·María V MencucciBárbara Maiztegui
Oct 23, 2020·Islets·Gerardo J Félix-MartínezJ Rafael Godínez-Fernández
Dec 16, 2020·Molecular and Cellular Biology·Jennifer M GilbertBarak Blum
Aug 29, 2020·Developmental Cell·Corinna CozzitortoFrancesca M Spagnoli

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Methods Mentioned

BETA
Assay

Software Mentioned

ImageJ
Prism 7 Graph Pad
Robo

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