MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas
Sara Bsharat, Emanuela Monni, Tania Singh, Jenny K. Johansson, Kavya Achanta, Ludivine Bertonnier‐Brouty, Anja Schmidt-Christensen, Dan Holmberg, Zaal Kokaia, Rashmi B. Prasad, Isabella Artner
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 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.