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MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas

Hormone secretion from pancreatic islets is essential for glucose homeostasis, and loss or dysfunction of islet cells is a hallmark of type 2 diabetes. Maf transcription factors are crucial for establishing and maintaining adult endocrine cell function. However, during pancreas development, MafB is...

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Autores principales: Bsharat, Sara, Monni, Emanuela, Singh, Tania, Johansson, Jenny K., Achanta, Kavya, Bertonnier-Brouty, Ludivine, Schmidt-Christensen, Anja, Holmberg, Dan, Kokaia, Zaal, Prasad, Rashmi B., Artner, Isabella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112931/
https://www.ncbi.nlm.nih.gov/pubmed/36897571
http://dx.doi.org/10.1242/dev.201009
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author Bsharat, Sara
Monni, Emanuela
Singh, Tania
Johansson, Jenny K.
Achanta, Kavya
Bertonnier-Brouty, Ludivine
Schmidt-Christensen, Anja
Holmberg, Dan
Kokaia, Zaal
Prasad, Rashmi B.
Artner, Isabella
author_facet Bsharat, Sara
Monni, Emanuela
Singh, Tania
Johansson, Jenny K.
Achanta, Kavya
Bertonnier-Brouty, Ludivine
Schmidt-Christensen, Anja
Holmberg, Dan
Kokaia, Zaal
Prasad, Rashmi B.
Artner, Isabella
author_sort Bsharat, Sara
collection PubMed
description Hormone secretion from pancreatic islets is essential for glucose homeostasis, and loss or dysfunction of islet cells is a hallmark of type 2 diabetes. Maf transcription factors are crucial for establishing and maintaining adult endocrine cell function. However, during pancreas development, MafB is not only expressed in insulin- and glucagon-producing cells, but also in Neurog3(+) endocrine progenitor cells, suggesting additional functions in cell differentiation and islet formation. Here, we report that MafB deficiency impairs β cell clustering and islet formation, but also coincides with loss of neurotransmitter and axon guidance receptor gene expression. Moreover, the observed loss of nicotinic receptor gene expression in human and mouse β cells implied that signaling through these receptors contributes to islet cell migration/formation. Inhibition of nicotinic receptor activity resulted in reduced β cell migration towards autonomic nerves and impaired β cell clustering. These findings highlight a novel function of MafB in controlling neuronal-directed signaling events required for islet formation.
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spelling pubmed-101129312023-04-19 MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas Bsharat, Sara Monni, Emanuela Singh, Tania Johansson, Jenny K. Achanta, Kavya Bertonnier-Brouty, Ludivine Schmidt-Christensen, Anja Holmberg, Dan Kokaia, Zaal Prasad, Rashmi B. Artner, Isabella Development Research Article Hormone secretion from pancreatic islets is essential for glucose homeostasis, and loss or dysfunction of islet cells is a hallmark of type 2 diabetes. Maf transcription factors are crucial for establishing and maintaining adult endocrine cell function. However, during pancreas development, MafB is not only expressed in insulin- and glucagon-producing cells, but also in Neurog3(+) endocrine progenitor cells, suggesting additional functions in cell differentiation and islet formation. Here, we report that MafB deficiency impairs β cell clustering and islet formation, but also coincides with loss of neurotransmitter and axon guidance receptor gene expression. Moreover, the observed loss of nicotinic receptor gene expression in human and mouse β cells implied that signaling through these receptors contributes to islet cell migration/formation. Inhibition of nicotinic receptor activity resulted in reduced β cell migration towards autonomic nerves and impaired β cell clustering. These findings highlight a novel function of MafB in controlling neuronal-directed signaling events required for islet formation. The Company of Biologists Ltd 2023-03-27 /pmc/articles/PMC10112931/ /pubmed/36897571 http://dx.doi.org/10.1242/dev.201009 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Bsharat, Sara
Monni, Emanuela
Singh, Tania
Johansson, Jenny K.
Achanta, Kavya
Bertonnier-Brouty, Ludivine
Schmidt-Christensen, Anja
Holmberg, Dan
Kokaia, Zaal
Prasad, Rashmi B.
Artner, Isabella
MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title_full MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title_fullStr MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title_full_unstemmed MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title_short MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
title_sort mafb-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112931/
https://www.ncbi.nlm.nih.gov/pubmed/36897571
http://dx.doi.org/10.1242/dev.201009
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