Neurogenin-3

NEUROG3
Identifiers
Aliases	NEUROG3, Atoh5, Math4B, NGN-3, bHLHa7, ngn3, neurogenin 3
External IDs	OMIM: 604882 MGI: 893591 HomoloGene: 40692 GeneCards: NEUROG3
Gene location (Human)
Chr.	Chromosome 10 (human)[1]
End	69,573,422 bp[1]
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)[2]
End	62,134,763 bp[2]
Gene ontology
Molecular function	• DNA binding; • protein dimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0001105 transcription coactivator activity; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • GO:0001948 protein binding; • double-stranded DNA binding; • chromatin DNA binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• cytoplasm; • intracellular; • cell nucleus;
Biological process	• neurogenesis; • cell differentiation; • peripheral nervous system development; • regulation of transcription, DNA-templated; • epithelial cell differentiation; • hindbrain development; • positive regulation of sequence-specific DNA binding transcription factor activity; • negative regulation of transcription from RNA polymerase II promoter; • transcription from RNA polymerase II promoter; • transcription, DNA-templated; • nervous system development; • regulation of dendrite morphogenesis; • multicellular organism development; • central nervous system development; • positive regulation of neuron differentiation; • positive regulation of cell differentiation; • spinal cord development; • forebrain development; • positive regulation of transcription from RNA polymerase II promoter; • transdifferentiation; • endocrine pancreas development;
	Sources:Amigo / QuickGO
Orthologs
	50674
	11925
	ENSG00000122859
	ENSMUSG00000044312
	Q9Y4Z2
	P70661
	NM_020999
	NM_009719
	NP_066279
	NP_033849
	Wikidata
View/Edit Human	View/Edit Mouse

Neurogenin-3 is a protein that in humans is encoded by the NEUROG3 gene.[5]

Neurogenin-3 is expressed in endocrine progenitor cells and is required for endocrine cell development in the pancreas and intestine.[6] It belongs to a family of basic helix-loop-helix (bHLH) transcription factors involved in the determination of neural precursor cells in the neuroectoderm.[7]

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.[8] Human[9] and rodent[10][11][12][13][14][15][16][17][18] 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.

Detail

Much more at Neurogenins#Neurogenin-3

References

GRCh38: Ensembl release 89: ENSG00000122859 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000044312 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: neurogenin 3".
Wang J, Cortina G, Wu SV, Tran R, Cho JH, Tsai MJ, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martín MG (Jul 2006). "Mutant neurogenin-3 in congenital malabsorptive diarrhea". The New England Journal of Medicine. 355 (3): 270–80. doi:10.1056/NEJMoa054288. PMID 16855267.
Gradwohl G, Dierich A, LeMeur M, Guillemot F (Feb 2000). "neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas". Proceedings of the National Academy of Sciences of the United States of America. 97 (4): 1607–11. Bibcode:2000PNAS...97.1607G. doi:10.1073/pnas.97.4.1607. PMC 26482. PMID 10677506.
Gomez DL, O'Driscoll M, Sheets TP, Hruban RH, Oberholzer J, McGarrigle JJ, Shamblott MJ (2015). "Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate". PLOS ONE. 10 (8): e0133862. Bibcode:2015PLoSO..1033862G. doi:10.1371/journal.pone.0133862. PMC 4545947. PMID 26288179.
Swales N, Martens GA, Bonné S, Heremans Y, Borup R, Van de Casteele M, Ling Z, Pipeleers D, Ravassard P, Nielsen F, Ferrer J, Heimberg H (2012). "Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming". PLOS ONE. 7 (5): e37055. Bibcode:2012PLoSO...737055S. doi:10.1371/journal.pone.0037055. PMC 3351393. PMID 22606327.
Xu X, D'Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H (Jan 2008). "Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas". Cell. 132 (2): 197–207. doi:10.1016/j.cell.2007.12.015. PMID 18243096. S2CID 8058714.
Van de Casteele M, Leuckx G, Baeyens L, Cai Y, Yuchi Y, Coppens V, De Groef S, Eriksson M, Svensson C, Ahlgren U, Ahnfelt-Rønne J, Madsen OD, Waisman A, Dor Y, Jensen JN, Heimberg H (7 March 2013). "Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas". Cell Death & Disease. 4 (3): e523. doi:10.1038/cddis.2013.52. PMC 3613830. PMID 23470530.
Figeac F, Ilias A, Bailbe D, Portha B, Movassat J (Oct 2012). "Local in vivo GSK3β knockdown promotes pancreatic β cell and acinar cell regeneration in 90% pancreatectomized rat". Molecular Therapy. 20 (10): 1944–52. doi:10.1038/mt.2012.112. PMC 3464647. PMID 22828498.
Li WC, Rukstalis JM, Nishimura W, Tchipashvili V, Habener JF, Sharma A, Bonner-Weir S (Aug 2010). "Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats". Journal of Cell Science. 123 (Pt 16): 2792–802. doi:10.1242/jcs.065268. PMC 2915881. PMID 20663919.
Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CV, Van de Casteele M, German MS, Bouwens L, Heimberg H (Jan 2014). "Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice". Nature Biotechnology. 32 (1): 76–83. doi:10.1038/nbt.2747. PMC 4096987. PMID 24240391.
Baeyens L, Bonné S, German MS, Ravassard P, Heimberg H, Bouwens L (Nov 2006). "Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway". Cell Death and Differentiation. 13 (11): 1892–9. doi:10.1038/sj.cdd.4401883. PMID 16514419.
Lemper M, Leuckx G, Heremans Y, German MS, Heimberg H, Bouwens L, Baeyens L (Jul 2015). "Reprogramming of human pancreatic exocrine cells to β-like cells". Cell Death and Differentiation. 22 (7): 1117–30. doi:10.1038/cdd.2014.193. PMC 4572860. PMID 25476775.
Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (Oct 2008). "In vivo reprogramming of adult pancreatic exocrine cells to beta-cells". Nature. 455 (7213): 627–32. Bibcode:2008Natur.455..627Z. doi:10.1038/nature07314. PMID 18754011. S2CID 205214877.
Sancho R, Gruber R, Gu G, Behrens A (Aug 2014). "Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells". Cell Stem Cell. 15 (2): 139–53. doi:10.1016/j.stem.2014.06.019. PMC 4136739. PMID 25105579.

Lejonklou MH, Edfeldt K, Johansson TA, Stålberg P, Skogseid B (Apr 2009). "Neurogenin 3 and neurogenic differentiation 1 are retained in the cytoplasm of multiple endocrine neoplasia type 1 islet and pancreatic endocrine tumor cells". Pancreas. 38 (3): 259–66. doi:10.1097/MPA.0b013e3181930818. PMID 19307926. S2CID 23414763.
del Bosque-Plata L, Lin J, Horikawa Y, Schwarz PE, Cox NJ, Iwasaki N, Ogata M, Iwamoto Y, German MS, Bell GI (Mar 2001). "Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects". Diabetes. 50 (3): 694–6. doi:10.2337/diabetes.50.3.694. PMID 11246894.
Cauchi S, Proença C, Choquet H, Gaget S, De Graeve F, Marre M, Balkau B, Tichet J, Meyre D, Vaxillaire M, Froguel P (Mar 2008). "Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study". Journal of Molecular Medicine. 86 (3): 341–8. doi:10.1007/s00109-007-0295-x. PMID 18210030. S2CID 21785287.
Jensen JN, Hansen L, Ekstrøm CT, Pociot F, Nerup J, Hansen T, Pedersen O (Jan 2001). "Polymorphisms in the neurogenin 3 gene (NEUROG) and their relation to altered insulin secretion and diabetes in the Danish Caucasian population". Diabetologia. 44 (1): 123–6. doi:10.1007/s001250051589. PMID 11206403.
Cauchi S, Meyre D, Durand E, Proença C, Marre M, Hadjadj S, Choquet H, De Graeve F, Gaget S, Allegaert F, Delplanque J, Permutt MA, Wasson J, Blech I, Charpentier G, Balkau B, Vergnaud AC, Czernichow S, Patsch W, Chikri M, Glaser B, Sladek R, Froguel P (2008). "Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value". PLOS ONE. 3 (5): e2031. Bibcode:2008PLoSO...3.2031C. doi:10.1371/journal.pone.0002031. PMC 2346547. PMID 18461161.
Louet JF, Smith SB, Gautier JF, Molokhia M, Virally ML, Kevorkian JP, Guillausseau PJ, Vexiau P, Charpentier G, German MS, Vaisse C, Urbanek M, Mauvais-Jarvis F (Sep 2008). "Gender and neurogenin3 influence the pathogenesis of ketosis-prone diabetes". Diabetes, Obesity & Metabolism. 10 (10): 912–20. doi:10.1111/j.1463-1326.2007.00830.x. PMID 18093211. S2CID 42776632.
Yokoi N, Kanamori M, Horikawa Y, Takeda J, Sanke T, Furuta H, Nanjo K, Mori H, Kasuga M, Hara K, Kadowaki T, Tanizawa Y, Oka Y, Iwami Y, Ohgawara H, Yamada Y, Seino Y, Yano H, Cox NJ, Seino S (Aug 2006). "Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects". Diabetes. 55 (8): 2379–86. doi:10.2337/db05-1203. PMID 16873704.
Milord E, Gragnoli C (Oct 2006). "NEUROG3 variants and type 2 diabetes in Italians". Minerva Medica. 97 (5): 373–8. PMID 17146417.
Li J, Bergmann A, Reimann M, Schulze J, Bornstein SR, Schwarz PE (Mar 2008). "Genetic variation of Neurogenin 3 is slightly associated with hyperproinsulinaemia and progression toward type 2 diabetes". Experimental and Clinical Endocrinology & Diabetes. 116 (3): 178–83. doi:10.1055/s-2007-992156. PMID 18072012.
Dror V, Nguyen V, Walia P, Kalynyak TB, Hill JA, Johnson JD (Dec 2007). "Notch signalling suppresses apoptosis in adult human and mouse pancreatic islet cells". Diabetologia. 50 (12): 2504–15. doi:10.1007/s00125-007-0835-5. PMID 17922104.
Heremans Y, Van De Casteele M, in't Veld P, Gradwohl G, Serup P, Madsen O, Pipeleers D, Heimberg H (Oct 2002). "Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3". The Journal of Cell Biology. 159 (2): 303–12. doi:10.1083/jcb.200203074. PMC 2173047. PMID 12403815.
Jackson AE, Cassell PG, North BV, Vijayaraghavan S, Gelding SV, Ramachandran A, Snehalatha C, Hitman GA (Aug 2004). "Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population". Diabetes. 53 (8): 2122–5. doi:10.2337/diabetes.53.8.2122. PMID 15277395.
Drenos F, Talmud PJ, Casas JP, Smeeth L, Palmen J, Humphries SE, Hingorani AD (Jun 2009). "Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk". Human Molecular Genetics. 18 (12): 2305–16. doi:10.1093/hmg/ddp159. PMC 2685759. PMID 19336475.
Okada T, Tobe K, Hara K, Yasuda K, Kawaguchi Y, Ikegami H, Ito C, Kadowaki T (Feb 2001). "Variants of neurogenin 3 gene are not associated with Type II diabetes in Japanese subjects". Diabetologia. 44 (2): 241–4. doi:10.1007/s001250051606. PMID 11270683.
Sommer L, Ma Q, Anderson DJ (1996). "neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS". Molecular and Cellular Neurosciences. 8 (4): 221–41. doi:10.1006/mcne.1996.0060. PMID 9000438. S2CID 21375109.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000122859 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000044312 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: neurogenin 3".

[pmid16855267-6] Wang J, Cortina G, Wu SV, Tran R, Cho JH, Tsai MJ, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martín MG (Jul 2006). "Mutant neurogenin-3 in congenital malabsorptive diarrhea". The New England Journal of Medicine. 355 (3): 270–80. doi:10.1056/NEJMoa054288. PMID 16855267.

[pmid10677506-7] Gradwohl G, Dierich A, LeMeur M, Guillemot F (Feb 2000). "neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas". Proceedings of the National Academy of Sciences of the United States of America. 97 (4): 1607–11. Bibcode:2000PNAS...97.1607G. doi:10.1073/pnas.97.4.1607. PMC 26482. PMID 10677506.

[8] Gomez DL, O'Driscoll M, Sheets TP, Hruban RH, Oberholzer J, McGarrigle JJ, Shamblott MJ (2015). "Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate". PLOS ONE. 10 (8): e0133862. Bibcode:2015PLoSO..1033862G. doi:10.1371/journal.pone.0133862. PMC 4545947. PMID 26288179.

[9] Swales N, Martens GA, Bonné S, Heremans Y, Borup R, Van de Casteele M, Ling Z, Pipeleers D, Ravassard P, Nielsen F, Ferrer J, Heimberg H (2012). "Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming". PLOS ONE. 7 (5): e37055. Bibcode:2012PLoSO...737055S. doi:10.1371/journal.pone.0037055. PMC 3351393. PMID 22606327.

[10] Xu X, D'Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H (Jan 2008). "Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas". Cell. 132 (2): 197–207. doi:10.1016/j.cell.2007.12.015. PMID 18243096. S2CID 8058714.

[11] Van de Casteele M, Leuckx G, Baeyens L, Cai Y, Yuchi Y, Coppens V, De Groef S, Eriksson M, Svensson C, Ahlgren U, Ahnfelt-Rønne J, Madsen OD, Waisman A, Dor Y, Jensen JN, Heimberg H (7 March 2013). "Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas". Cell Death & Disease. 4 (3): e523. doi:10.1038/cddis.2013.52. PMC 3613830. PMID 23470530.

[12] Figeac F, Ilias A, Bailbe D, Portha B, Movassat J (Oct 2012). "Local in vivo GSK3β knockdown promotes pancreatic β cell and acinar cell regeneration in 90% pancreatectomized rat". Molecular Therapy. 20 (10): 1944–52. doi:10.1038/mt.2012.112. PMC 3464647. PMID 22828498.

[13] Li WC, Rukstalis JM, Nishimura W, Tchipashvili V, Habener JF, Sharma A, Bonner-Weir S (Aug 2010). "Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats". Journal of Cell Science. 123 (Pt 16): 2792–802. doi:10.1242/jcs.065268. PMC 2915881. PMID 20663919.

[14] Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CV, Van de Casteele M, German MS, Bouwens L, Heimberg H (Jan 2014). "Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice". Nature Biotechnology. 32 (1): 76–83. doi:10.1038/nbt.2747. PMC 4096987. PMID 24240391.

[15] Baeyens L, Bonné S, German MS, Ravassard P, Heimberg H, Bouwens L (Nov 2006). "Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway". Cell Death and Differentiation. 13 (11): 1892–9. doi:10.1038/sj.cdd.4401883. PMID 16514419.

[16] Lemper M, Leuckx G, Heremans Y, German MS, Heimberg H, Bouwens L, Baeyens L (Jul 2015). "Reprogramming of human pancreatic exocrine cells to β-like cells". Cell Death and Differentiation. 22 (7): 1117–30. doi:10.1038/cdd.2014.193. PMC 4572860. PMID 25476775.

[17] Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (Oct 2008). "In vivo reprogramming of adult pancreatic exocrine cells to beta-cells". Nature. 455 (7213): 627–32. Bibcode:2008Natur.455..627Z. doi:10.1038/nature07314. PMID 18754011. S2CID 205214877.

[18] Sancho R, Gruber R, Gu G, Behrens A (Aug 2014). "Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells". Cell Stem Cell. 15 (2): 139–53. doi:10.1016/j.stem.2014.06.019. PMC 4136739. PMID 25105579.

Neurogenin-3

Detail

References

Further reading