Pancreatic islets consist of endocrine cells including α and β cells, and dysfunction of the latter can lead to diabetes mellitus. The transcription factor MafB is required for α and β cell terminal differentiation in mice. MafB expression has also been detected in endocrine progenitor cells, suggesting that it may play an additional role at an earlier stage. Here, Isabella Artner, Rashmi Prasad and colleagues show that MafB mutant mice exhibit disrupted islet morphology compared with their wild-type peers. Global gene expression analysis reveals that MafB loss in endocrine progenitors results in an unexpected reduction in neurotransmitter and axon guidance receptor gene expression. By analysing single-cell sequencing data, they find that these receptor genes are expressed in the β progenitor cells of both mice and humans. These novel MafB targets include nicotinic receptors, and the authors show that pharmacologically blocking nicotinic signalling inhibits β cell migration towards developing parasympathetic nerves. Overall, these findings reveal a novel role for MafB in modulating β cell neurotransmitter sensing, which could have implications for proper islet formation and innervation, and could help to explain a previously described association between prenatal nicotine exposure and increased type 2 diabetes risk.