Neuronal development program in pancreatic beta-cell differentiation

It has been shown that gene expression patterns in pancreatic beta-cells have numerous similarities with neurons due to their common evolutionary ancestor. Gene ontology analyses also revealed the pancreatic endocrine cell development is enriched by sets of genes known in neuronal differentiation. Hypothalamus, retina and motor neurons possess molecular characteristics highly resemble beta-cells among all regions of the nervous systems. Neurons in the arcuate nucleus (ARC) of the hypothalamus are the major contributors to energy homeostasis and glucose metabolism in the brain. In hypothalamic nuclei, particularly ARC, the involvement of transcription factors including Neurogenin3, Neurod1, Ascl1 and Isl1 during development, is closely similar to the role of mentioned transcription factors in beta-cell development. Like retina, bHLH transcription factors triggers commitment of pancreas endocrine progenitors to generate different endocrine cell types at different stages, a phenomenon that is called the competence model. A good example that could represent the molecular characteristics common to beta-cells and motor neurons is the mutation in gene Mnx1 that causes neonatal diabetes and aberrant motor neuron differentiation. Additionally, in recent studies, the role of Nkx6.1 as an early marker is under further investigations to be used in the refinement of beta-like cells and motor neurons differentiation protocol. In this review, we aim to find out about shared transcription factors between pancreatic beta-cells and neurons in hypothalamus and retina with respect to their developmental stages. This understanding would help us to use successful methods of producing neurons from stem cells for improving the differentiation and function of beta-like cells.

کلیدواژه ها:

Neuronal development ، Pancreatic beta-cell ، Differentiation