Morphogenesis of the islets of langerhans is guided by extraendocrine Slit2 and Slit3 signals

Jennifer M. Gilbert, Melissa T. Adams, Nadav Sharon, Hariharan Jayaraaman, Barak Blum

Research output: Contribution to journalArticlepeer-review

Abstract

The spatial architecture of the islets of Langerhans is vitally important for their correct function, and alterations in islet morphogenesis often result in diabetes mellitus. We have previously reported that Roundabout (Robo) receptors are required for proper islet morphogenesis. As part of the Slit-Robo signaling pathway, Robo receptors function in conjunction with Slit ligands to mediate axon guidance, cell migration, and cell positioning in development. However, the role of Slit ligands in islet morphogenesis has not yet been determined. Here, we report that Slit ligands are expressed in overlapping and distinct patterns in both endocrine and nonendocrine tissues in late pancreas development. We show that the function of either Slit2 or Slit3, which are predominantly expressed in the pancreatic mesenchyme, is required and sufficient for islet morphogenesis, while Slit1, which is predominantly expressed in the b cells, is dispensable for islet morphogenesis. We further show that Slit functions as a repellent signal to b cells. These data suggest that clustering of endocrine cells during islet morphogenesis is guided, at least in part, by repelling Slit2/3 signals from the pancreatic mesenchyme.

Original languageEnglish
Article numbere00451-20
JournalMolecular and Cellular Biology
Volume41
Issue number3
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Islets of Langerhans
  • Pancreas development
  • Slit-Robo

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Morphogenesis of the islets of langerhans is guided by extraendocrine Slit2 and Slit3 signals'. Together they form a unique fingerprint.

Cite this