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Neurogenin-3 is a protein that in humans is encoded by the NEUROG3 gene.

Neurogenin-3 is expressed in endocrine progenitor cells and is required for endocrine cell development in the pancreas and intestine. It belongs to a family of basic helix-loop-helix (bHLH) transcription factors involved in the determination of neural precursor cells in the neuroectoderm.

Neurogenin 3 (NGN3) is expressed by 2-10% of acinar and duct cells in the histologically normal adult human pancreas. NGN3+ cells isolated from cultured exocrine tissue by coexpressed cell surface glycoprotein CD133 have a transcriptome consistent with exocrine dedifferentiation, a phenotype that resembles endocrine progenitor cells during development, and a capacity for endocrine differentiation in vitro. Human and rodent exocrine cells have been reprogrammed into cells with an islet cell-like phenotype following direct expression of NGN3 or manipulation that leads to its expression.

Neurogenin-3(NGN3) is a pro-endocrine transcription factor encoded by the Neurog3 gene in humans. It is a member of the basic helix-loop-helix (bHLH) transcription factor and has a primary function of activating gene transcription in endocrine progenitor cells. It is a master regulator of pancreatic islet differentiation and regeneration and functions to directly enhance the expression of the lineage-committed transcription factors required for the differentiation of the endocrine progenitor cells into each of the endocrine cell subtypes.

Expression
Neurogenin3 is expressed in a small percentage of cells within the developing pancreas consisting of endocrine progenitor cells. It is expressed in the three stages of the development and differentiation of the endocrine pancreas. These stages are termed the


 * 1) First or primary transition stage which involves the specification and growth of a primitive stalk of primarily undifferentiated pancreatic epithelial cells, originating from two separate sites along the gut tube which later fuse to become a single organ.
 * 2) Second transition stage which is the period when the majority of endocrine cell differentiation occurs and the growing stalk of uncommitted pancreatic progenitors undergoes a branching morphogenesis and extensive endocrine and exocrine cytodifferentiation occurs and finally.
 * 3) Third transition stage where the individual differentiated endocrine cells (α,β,δ and PP cells) migrate away from the progenitor cell domain at the core of the developing pancreas and coalesce into islets of Langerhans.

The significance of NGN3 in endocrine cell development is shown by the fact that Neurog3 deficiency prevents the generation of all pancreatic and intestinal endocrine cells. Interestingly, ectopic overexpression of Neurog3 leads to reduced endocrine mass as well, but by a mechanism that is different from that of  Neurog3 deficiency. Overexpression of Neurog3 throughout the uncommitted pancreatic progenitor domain induces premature differentiation of the progenitor cell population into the endocrine lineage, effectively depleting the pool of multi-potent progenitor cells prior to their expansion resulting in a reduction in the overall mass of pancreatic endocrine tissue. These data point at a tight regulation of Neurog3 expression to maintain the proper size and cell composition of the endocrine pancreas.

Genetic mutations in Neurogenin3 have been often found to cause neonatal diabetes and the significance of neurogenin3 has also been further shown using invitro analysis where neurogenin3 was found to required for the development of mature human beta cells from pluripotent stem cells.