MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
(2023) In Development: For advances in developmental biology and stem cells 150(6).- Abstract
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 critical 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 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... (More)
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 critical 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 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.
(Less)
- author
- organization
-
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Endocrine Cell Differentiation and Function (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Stem Cells & Restorative Neurology (research group)
- Neural stem cell biology and therapy (research group)
- Diabetes - Molecular Metabolism (research group)
- Stem Cell Center
- Diabetic Complications (research group)
- Autoimmunity (research group)
- Translational Muscle Research (research group)
- Imaging
- publishing date
- 2023-03-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Development: For advances in developmental biology and stem cells
- volume
- 150
- issue
- 6
- article number
- dev201009
- publisher
- The Company of Biologists Ltd
- external identifiers
-
- pmid:36897571
- scopus:85151044363
- ISSN
- 0950-1991
- DOI
- 10.1242/dev.201009
- language
- English
- LU publication?
- yes
- id
- c1f30173-a4d4-49a0-8373-d9528c184f16
- date added to LUP
- 2023-03-12 14:18:07
- date last changed
- 2024-09-21 10:40:15
@article{c1f30173-a4d4-49a0-8373-d9528c184f16, abstract = {{<p>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 critical 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 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.</p>}}, author = {{Bsharat, Sara and Monni, Emanuela and Singh, Tania and Johansson, Jenny K and Achanta, Kavya and Bertonnier-Brouty, Ludivine and Schmidt-Christensen, Anja and Holmberg, Dan and Kokaia, Zaal and Prasad, Rashmi B and Artner, Isabella}}, issn = {{0950-1991}}, language = {{eng}}, month = {{03}}, number = {{6}}, publisher = {{The Company of Biologists Ltd}}, series = {{Development: For advances in developmental biology and stem cells}}, title = {{MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas}}, url = {{http://dx.doi.org/10.1242/dev.201009}}, doi = {{10.1242/dev.201009}}, volume = {{150}}, year = {{2023}}, }