RT Journal Article
SR Electronic
T1 Morphogenesis of the islets of Langerhans is guided by extra-endocrine Slit2/3 signals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.15.153353
DO 10.1101/2020.06.15.153353
A1 Jennifer M. Gilbert
A1 Melissa T. Adams
A1 Nadav Sharon
A1 Hariharan Jayaraaman
A1 Barak Blum
YR 2020
UL http://biorxiv.org/content/early/2020/06/16/2020.06.15.153353.abstract
AB 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 function of Roundabout (Robo) receptors, selectively in β-cells, is required for proper islet morphogenesis. As part of the Slit-Robo signaling pathway, Robo receptors work 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 non-endocrine tissues in late pancreas development. We show that 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 endocrine compartment, is dispensable for islet morphogenesis. We further provide evidence to suggest that Slit-Robo signaling in the pancreas influences endocrine cell-cell adhesion, not cell migration, during islet morphogenesis. These data add important understanding to the fundamental question of the formation of the unique architecture of the islets of Langerhans.