Disease relevance of NEUROG3

• These polymorphisms were not associated with MODY, thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in Japanese patients [1].
• We have developed an in vitro model of Ngn3-dependent differentiation by infecting pancreatic duct cell lines with an Ngn3-expressing adenovirus [2].
• We delivered Pdx-1 and Ngn3 to the livers of diabetic mice using adeno-associated virus (AAV) serotype 8, a vector that has been shown to result in non-toxic, persistent, high level expression of the transgene [3].
• We were unable to correct hyperglycemia in mice with streptozotocin-induced diabetes using AAV vectors expressing Pdx-1 and Ngn3 [3].

High impact information on NEUROG3

• Similarly, ngn3 is transiently expressed in the developing pancreas and a knockout results in the absence of endocrine cells [4].
• Using in ovo electroporation of chick embryos, we show that ectopic expression of Pdx-1 or ngn3 causes cells to bud out of the epithelium like pancreatic progenitors [4].
• Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3 [5].
• Monoclonal antibodies that recognize cell-surface proteins on candidate stem cells in brain, skin, and other organs enabled separation of major pancreatic cell lineages and isolation of native pancreatic cells expressing neurogenin 3, an established marker of islet progenitors [6].
• These studies demonstrate how Ngn3 initiates islet differentiation and provide us with a model for testing methods for producing islet cells for people with diabetes [2].

Biological context of NEUROG3

• Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3 [7].
• The defect is secondary to point mutations in NEUROG3, which result in an arrest of endocrine cell development in the small intestine and colon [8].
• CONCLUSIONS: The biological impact of NEUROG3 might be due to the presence of either CCCAGT at 44-45nt, 167Arg, 199Ser or by a haplotype combination of these 3 or 2 of them [9].
• A potential candidate gene for T2D is Neurogenin 3 (Ngn3, NEUROG3), which lies on chromosome 10 in a region with several potential linkage signals to T2D in various population studies [9].
• In addition, microarray gene expression analysis identified a previously uncharacterized group of Ngn3-induced genes with potentially important roles in islet development and function [2].

Anatomical context of NEUROG3

• BACKGROUND: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine [10].
• METHODS: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3 [10].
• Because neurogenin 3 is required for the development of beta-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene [1].
• Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population [11].
• The HLH domain is also the characteristic of the bHLH family, which implied a large number of PTDs could be discovered in this family to fit different purposes, and some of them could be directly recruited to penetrate cell membrane according to their crucial roles in development such as NeuroD and Ngn3 [12].

Associations of NEUROG3 with chemical compounds

• An mESC line was created in order to induce Ngn3 by adding doxycycline to the culture medium [13].

Other interactions of NEUROG3

• p38 MAPK is involved in activin A- and hepatocyte growth factor-mediated expression of pro-endocrine gene neurogenin 3 in AR42J-B13 cells [14].
• RFX3 expression already is evident in early Ngn3-positive progenitors and is maintained in all major pancreatic endocrine cell lineages throughout their development [15].
• To better understand how Neurogenin3 directs endocrine differentiation, we examined the mechanisms by which Neurogenin3 regulates the promoters of three transcription factor genes expressed in endocrine precursor cells: the nkx2.2 gene, the PAX4 gene, and the NEUROG3 gene, the human gene encoding Neurogenin3 itself [16].
• Furthermore, ectopic Mfng expression induces the expression of basic helix-loop-helix gene, Ngn3, and two zinc finger genes, cMyt1 and cMyt3 [17].
• Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p < .0001) when compared with uninduced EBs [13].

Analytical, diagnostic and therapeutic context of NEUROG3

• Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of contexts, including undifferentiated ESCs and differentiating embryoid bodies (EBs) [13].
• Using degenerate PCR, the P. obesus Neurogenin-3 (Ngn-3) gene was cloned [18].
• Using a zebrafish radiation hybrid panel, ngn3 was mapped to zebrafish linkage group 13 and the region displayed a conserved synteny with the region of human chromosome 10 containing NGN3 [19].

References