TY - JOUR
T1 - Morphogenesis of the islets of langerhans is guided by extraendocrine Slit2 and Slit3 signals
AU - Gilbert, Jennifer M.
AU - Adams, Melissa T.
AU - Sharon, Nadav
AU - Jayaraaman, Hariharan
AU - Blum, Barak
N1 - Publisher Copyright: Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2020
Y1 - 2020
N2 - 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.
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 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.
KW - Islets of Langerhans
KW - Pancreas development
KW - Slit-Robo
UR - http://www.scopus.com/inward/record.url?scp=85103093633&partnerID=8YFLogxK
U2 - https://doi.org/10.1128/MCB.00451-20
DO - https://doi.org/10.1128/MCB.00451-20
M3 - مقالة
C2 - 33318057
SN - 0270-7306
VL - 41
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 3
M1 - e00451-20
ER -