NEUROD1 explained

Neurogenic differentiation 1 (Neurod1), also called β2,^[1] is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.

In mice, Neurod1 expression is first seen at embryonic day 12 (E12).^[2]

It is a member of the Neurod family of basic helix-loop-helix (bHLH) transcription factors, composed of Neurod1, Neurod2, Neurod4, and Neurod6. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus in mouse models and in human clinical patients.^[3]

Neurod1 is found to convert reactive glial cells into functional neurons in the mouse brain in vivo^[4] In the adult cortex, Neurod1 expression is a marker of mature excitatory pyramidal neurons in the upper-most layers of the cortex.^[5]

Interactions

Neurod1 has been shown to interact with MAP3K10,^[6] MAFA^[7] and Cyclin D1.^[8]

References

Further reading

• Fajans SS, Bell GI, Polonsky KS . Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young . The New England Journal of Medicine . 345 . 13 . 971–980 . September 2001 . 11575290 . 10.1056/NEJMra002168 .
• Cho JH, Tsai MJ . The role of BETA2/NeuroD1 in the development of the nervous system . Molecular Neurobiology . 30 . 1 . 35–47 . August 2004 . 15247487 . 10.1385/MN:30:1:035 . Ming-Jer Tsai . 19923393 .
• Chae JH, Stein GH, Lee JE . NeuroD: the predicted and the surprising . Molecules and Cells . 18 . 3 . 271–288 . December 2004 . 15650322 . 10.1016/S1016-8478(23)13113-X . free .
• Tamimi R, Steingrimsson E, Copeland NG, Dyer-Montgomery K, Lee JE, Hernandez R, Jenkins NA, Tapscott SJ . The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2 . Genomics . 34 . 3 . 418–421 . June 1996 . 8786144 . 10.1006/geno.1996.0306 .
• Yokoyama M, Nishi Y, Miyamoto Y, Nakamura M, Akiyama K, Matsubara K, Okubo K . Molecular cloning of a human neuroD from a neuroblastoma cell line specifically expressed in the fetal brain and adult cerebellum . Brain Research. Molecular Brain Research . 42 . 1 . 135–139 . November 1996 . 8915591 . 10.1016/S0169-328X(96)00154-4 .
• Yokoyama M, Nishi Y, Yoshii J, Okubo K, Matsubara K . Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles . DNA Research . 3 . 5 . 311–320 . October 1996 . 9039501 . 10.1093/dnares/3.5.311 . free .
• Acharya HR, Dooley CM, Thoreson WB, Ahmad I . cDNA cloning and expression analysis of NeuroD mRNA in human retina . Biochemical and Biophysical Research Communications . 233 . 2 . 459–463 . April 1997 . 9144558 . 10.1006/bbrc.1997.6483 .
• Poulin G, Turgeon B, Drouin J . NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene . Molecular and Cellular Biology . 17 . 11 . 6673–6682 . November 1997 . 9343431 . 232521 . 10.1128/mcb.17.11.6673 .
• Furuta H, Horikawa Y, Iwasaki N, Hara M, Sussel L, Le Beau MM, Davis EM, Ogata M, Iwamoto Y, German MS, Bell GI . Beta-cell transcription factors and diabetes: mutations in the coding region of the BETA2/NeuroD1 (NEUROD1) and Nkx2.2 (NKX2B) genes are not associated with maturity-onset diabetes of the young in Japanese . Diabetes . 47 . 8 . 1356–1358 . August 1998 . 9703340 . 10.2337/diabetes.47.8.1356 .
• Yoon YS, Noma T, Yamashiro Y, Ito H, Nakazawa A . Molecular cloning and characterization of the gene encoding human NeuroD . Neuroscience Letters . 251 . 1 . 17–20 . July 1998 . 9714454 . 10.1016/S0304-3940(98)00490-X . 39872130 .
• Miyachi T, Maruyama H, Kitamura T, Nakamura S, Kawakami H . Structure and regulation of the human NeuroD (BETA2/BHF1) gene . Brain Research. Molecular Brain Research . 69 . 2 . 223–231 . June 1999 . 10366743 . 10.1016/S0169-328X(99)00112-6 .
• Noma T, Yoon YS, Yamashiro Y, Fujisawa K, Nakazawa A . Regulation of NeuroD expression by activation of the protein kinase-C pathway in Y79 human retinoblastoma cells . Neuroscience Letters . 272 . 1 . 45–48 . September 1999 . 10507539 . 10.1016/S0304-3940(99)00569-8 . 3158332 .
• Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram JH, Montminy M, Krolewski AS . Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus . Nature Genetics . 23 . 3 . 323–328 . November 1999 . 10545951 . 10.1038/15500 . 3216136 .
• Glick E, Leshkowitz D, Walker MD . Transcription factor BETA2 acts cooperatively with E2A and PDX1 to activate the insulin gene promoter . The Journal of Biological Chemistry . 275 . 3 . 2199–2204 . January 2000 . 10636926 . 10.1074/jbc.275.3.2199 . free .
• Onions J, Hermann S, Grundström T . A novel type of calmodulin interaction in the inhibition of basic helix-loop-helix transcription factors . Biochemistry . 39 . 15 . 4366–4374 . April 2000 . 10757985 . 10.1021/bi992533u .
• Mochizuki M, Amemiya S, Kobayashi K, Kobayashi K, Ishihara T, Aya M, Kato K, Kasuga A, Nakazawa S . The association of Ala45Thr polymorphism in NeuroD with child-onset Type 1a diabetes in Japanese . Diabetes Research and Clinical Practice . 55 . 1 . 11–17 . January 2002 . 11755474 . 10.1016/S0168-8227(01)00242-X .
• Ratineau C, Petry MW, Mutoh H, Leiter AB . Cyclin D1 represses the basic helix-loop-helix transcription factor, BETA2/NeuroD . The Journal of Biological Chemistry . 277 . 11 . 8847–8853 . March 2002 . 11788592 . 10.1074/jbc.M110747200 . free .
• Westerman BA, Poutsma A, Maruyama K, Schrijnemakers HF, van Wijk IJ, Oudejans CB . The proneural genes NEUROD1 and NEUROD2 are expressed during human trophoblast invasion . Mechanisms of Development . 113 . 1 . 85–90 . April 2002 . 11900979 . 10.1016/S0925-4773(01)00665-7 . 11607202 .
• Kanatsuka A, Tokuyama Y, Nozaki O, Matsui K, Egashira T . Beta-cell dysfunction in late-onset diabetic subjects carrying homozygous mutation in transcription factors NeuroD1 and Pax4 . Metabolism . 51 . 9 . 1161–1165 . September 2002 . 12200761 . 10.1053/meta.2002.34707 .

Notes and References

1. Poulin G, Turgeon B, Drouin J . NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene . Molecular and Cellular Biology . 17 . 11 . 6673–6682 . November 1997 . 9343431 . 232521 . 10.1128/mcb.17.11.6673 .
2. Bormuth I, Yan K, Yonemasu T, Gummert M, Zhang M, Wichert S, Grishina O, Pieper A, Zhang W, Goebbels S, Tarabykin V, Nave KA, Schwab MH . Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions . The Journal of Neuroscience . 33 . 2 . 641–651 . January 2013 . 23303943 . 6704922 . 10.1523/JNEUROSCI.0899-12.2013 . 25600245 . free .
3. Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram JH, Montminy M, Krolewski AS . Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus . Nature Genetics . 23 . 3 . 323–328 . November 1999 . 10545951 . 10.1038/15500 . 3216136 .
4. Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G . In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model . Cell Stem Cell . 14 . 2 . 188–202 . February 2014 . 24360883 . 3967760 . 10.1016/j.stem.2013.12.001 .
5. Tutukova S, Tarabykin V, Hernandez-Miranda LR . The Role of Neurod Genes in Brain Development, Function, and Disease . Frontiers in Molecular Neuroscience . 14 . 662774 . 2021 . 34177462 . 8221396 . 10.3389/fnmol.2021.662774 . free .
6. Marcora E, Gowan K, Lee JE . Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 . Proceedings of the National Academy of Sciences of the United States of America . 100 . 16 . 9578–9583 . August 2003 . 12881483 . 170960 . 10.1073/pnas.1133382100 . free . 2003PNAS..100.9578M .
7. Zhao L, Guo M, Matsuoka TA, Hagman DK, Parazzoli SD, Poitout V, Stein R . The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription . The Journal of Biological Chemistry . 280 . 12 . 11887–11894 . March 2005 . 15665000 . 10.1074/jbc.M409475200 . free .
8. Ratineau C, Petry MW, Mutoh H, Leiter AB . Cyclin D1 represses the basic helix-loop-helix transcription factor, BETA2/NeuroD . The Journal of Biological Chemistry . 277 . 11 . 8847–8853 . March 2002 . 11788592 . 10.1074/jbc.M110747200 . free .