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Gene Review

Neurod1  -  neurogenic differentiation 1

Mus musculus

Synonyms: BETA2, BHF-1, Beta-cell E-box transcriptional activator 2, Beta2, NeuroD1, ...
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Disease relevance of Neurod1


Psychiatry related information on Neurod1

  • We show that, in the beta2-/- mutant, the high-order spatiotemporal organization of locomotor behavior, together with conflict resolution and social interaction, is selectively dissociated from low-level, more automatic motor behaviors [6].
  • Mice lacking either the alpha1 or beta 2 subunit of the GABAA receptor were tested for ethanol, saccharin, or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and handling-induced seizures following chronic consumption of an ethanol liquid diet [7].
  • It is concluded that nicotinic receptors containing the beta2 subunit play a major role in the discriminative stimulus and taste aversion effects of nicotine that may reflect psychological aspects of tobacco dependence [8].
  • CONCLUSIONS: At concentrations assumed to cause sedation and amnesia, etomidate depresses theta oscillations via beta2-containing GABAA receptors but enhances these oscillations by acting on beta3 subunit containing receptors [9].
  • Nicotine (1-2 mg/kg, i.p.) increased wakefulness in wild-type but not knock-out animals, indicating that beta2-containing nAChRs mediate the arousing properties of nicotine [10].

High impact information on Neurod1

  • NK1 T cells express a restricted TCR repertoire made of an invariant TCR alpha chain, V alpha 14-J alpha 281, associated with polyclonal V beta 8, V beta 7, and V beta 2 TCR beta chains [11].
  • These lesions were prevented by treatment with a beta2 integrin antagonist [12].
  • The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Tr beta 2 in the commitment to an M-cone identity [13].
  • The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy [14].
  • In mice homozygous for a targeted disruption of Neurod, pancreatic islet morphogenesis is abnormal and overt diabetes develops due in part to inadequate expression of the insulin gene (Ins2) [15].

Chemical compound and disease context of Neurod1


Biological context of Neurod1


Anatomical context of Neurod1

  • Furthermore, overexpression of ngn3 could cause a dose-dependent activation on the 1.0-kb BETA2 promoter in islet-derived cell lines [23].
  • Based on these results, we hypothesize that ngn3 is involved in activating the expression of BETA2 at an early stage of islet cell differentiation through the E boxes in the BETA2 promoter [23].
  • The objective of this study is to identify potential upstream regulators of the BETA2 gene during pancreas development [23].
  • Laminar organization of the mouse dentate gyrus: insights from BETA2/Neuro D mutant mice [26].
  • The ability of BETA2/NeuroD and NDRF to convert ectodermal cells into neurons after mRNA injection into Xenopus oocytes suggested a role in specifying neuronal cell fate [27].

Associations of Neurod1 with chemical compounds

  • Although several transcription factors including Beta-2, Ribe3b1, and Pdx-1 have been shown to play a role in glucose stimulation of insulin gene expression, the exact molecular mechanism(s) by which this regulation occurs is unknown [28].
  • We previously reported that human PMNs stimulated in vitro adhere to laminin, the major glycoprotein of mammalian basement membrane, by both CD11/CD18 (beta 2 integrin)-dependent and CD11/CD18-independent mechanisms [29].
  • The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration [30].
  • Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance [31].
  • For evaluation of this concept we applied the bisindolylmaleimide GF 109203X, which shows a highly selective inhibition of PKC isozymes alpha, beta 1, beta 2, gamma, delta and epsilon in vitro [32].

Physical interactions of Neurod1

  • Thus, in the local reaction, the stimulation with LPS and tumor necrosis factor alpha leads to a binding of platelets to the endothelium of venules by their beta 2 integrins, which seems necessary for the development of the hemorrhagic necrosis [33].
  • RACK1 binds to a signal transfer region of G betagamma and inhibits phospholipase C beta2 activation [34].
  • There were corresponding reductions in the levels of alpha1 and beta2 subunit proteins and in autoradiographic ligand binding densities to GABA(A) receptors in the forebrain of alpha6-/- mice [35].
  • Identification of a functional NF-kappa B binding site in the murine T cell receptor beta 2 locus [36].
  • (5) the TcR alpha 3 loop interacts with the central portion of the peptide and stacks against the beta 2 loop [37].

Enzymatic interactions of Neurod1


Regulatory relationships of Neurod1


Other interactions of Neurod1

  • Furthermore, early expression of neurogenin3 under control of the Pdx1 promoter is alone sufficient to drive early and ectopic differentiation of islet cells, a capability shared by the pancreatic bHLH factor, neuroD1/BETA2, but not by the muscle bHLH factor, MyoD [42].
  • Re-plating the spheres onto an adhesive substrate and withdrawal of the growth factors induced the expression of mRNAs for NeuroD and Olig2 and generated more beta-III tubulin-positive cells [43].
  • Following transfection, PDX-1, ngn3, beta 2, and Nkx2.2 were expressed in F9-RAC cells, with their proteins localized mainly in cellular nuclei [44].
  • Our data suggest that Neurod-Btc gene therapy is a promising regimen to induce islet neogenesis for the treatment of insulin-dependent diabetes [45].
  • BETA2 plays an important role in the development of the pancreas and the nervous system [24].

Analytical, diagnostic and therapeutic context of Neurod1


  1. Requirement of multiple basic helix-loop-helix genes for retinal neuronal subtype specification. Akagi, T., Inoue, T., Miyoshi, G., Bessho, Y., Takahashi, M., Lee, J.E., Guillemot, F., Kageyama, R. J. Biol. Chem. (2004) [Pubmed]
  2. E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation. Kruyt, F.A., Folkers, G.E., Walhout, A.J., van der Leede, B.J., van der Saag, P.T. Mol. Endocrinol. (1993) [Pubmed]
  3. Alterations in protein kinase C isozymes alpha and beta 2 in activated Ha-ras containing papillomas in the absence of an increase in diacylglycerol. Mills, K.J., Bocckino, S.B., Burns, D.J., Loomis, C.R., Smart, R.C. Carcinogenesis (1992) [Pubmed]
  4. Glycogen synthase kinase 3beta together with 14-3-3 protein regulates diabetic cardiomyopathy: effect of losartan and tempol. Gurusamy, N., Watanabe, K., Ma, M., Prakash, P., Hirabayashi, K., Zhang, S., Muslin, A.J., Kodama, M., Aizawa, Y. FEBS Lett. (2006) [Pubmed]
  5. Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit of the neuronal nicotinic acetylcholine receptor. Harrist, A., Beech, R.D., King, S.L., Zanardi, A., Cleary, M.A., Caldarone, B.J., Eisch, A., Zoli, M., Picciotto, M.R. Synapse (2004) [Pubmed]
  6. Executive and social behaviors under nicotinic receptor regulation. Granon, S., Faure, P., Changeux, J.P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. GABAA receptor alpha 1 and beta 2 subunit null mutant mice: behavioral responses to ethanol. Blednov, Y.A., Walker, D., Alva, H., Creech, K., Findlay, G., Harris, R.A. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  8. The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion. Shoaib, M., Gommans, J., Morley, A., Stolerman, I.P., Grailhe, R., Changeux, J.P. Neuropharmacology (2002) [Pubmed]
  9. Opposing actions of etomidate on cortical theta oscillations are mediated by different gamma-aminobutyric acid type A receptor subtypes. Drexler, B., Roether, C.L., Jurd, R., Rudolph, U., Antkowiak, B. Anesthesiology (2005) [Pubmed]
  10. Beta2-containing nicotinic receptors contribute to the organization of sleep and regulate putative micro-arousals in mice. Léna, C., Popa, D., Grailhe, R., Escourrou, P., Changeux, J.P., Adrien, J. J. Neurosci. (2004) [Pubmed]
  11. Mouse CD1-specific NK1 T cells: development, specificity, and function. Bendelac, A., Rivera, M.N., Park, S.H., Roark, J.H. Annu. Rev. Immunol. (1997) [Pubmed]
  12. M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage. Herwald, H., Cramer, H., Mörgelin, M., Russell, W., Sollenberg, U., Norrby-Teglund, A., Flodgaard, H., Lindbom, L., Björck, L. Cell (2004) [Pubmed]
  13. A thyroid hormone receptor that is required for the development of green cone photoreceptors. Ng, L., Hurley, J.B., Dierks, B., Srinivas, M., Saltó, C., Vennström, B., Reh, T.A., Forrest, D. Nat. Genet. (2001) [Pubmed]
  14. The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy. De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. Nat. Genet. (2000) [Pubmed]
  15. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Malecki, M.T., Jhala, U.S., Antonellis, A., Fields, L., Doria, A., Orban, T., Saad, M., Warram, J.H., Montminy, M., Krolewski, A.S. Nat. Genet. (1999) [Pubmed]
  16. Role of oncogenes and tumor suppressor genes in multistage carcinogenesis. Yuspa, S.H., Długosz, A.A., Cheng, C.K., Denning, M.F., Tennenbaum, T., Glick, A.B., Weinberg, W.C. J. Invest. Dermatol. (1994) [Pubmed]
  17. Effects of a beta 3-adrenoceptor agonist, BRL 26830A, on insulin and glucagon release in mice. Yoshida, T., Hiraoka, N., Kondo, M. Endocrinol. Jpn. (1991) [Pubmed]
  18. beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure. Cohen, G., Han, Z.Y., Grailhe, R., Gallego, J., Gaultier, C., Changeux, J.P., Lagercrantz, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  19. Expression of the protein tyrosine phosphatase beta2 gene in mouse erythroleukemia cells induces terminal erythroid differentiation. Kume, T., Watanabe, T., Sanokawo, R., Chida, D., Nakamura, T., Oishi, M. J. Biol. Chem. (1996) [Pubmed]
  20. Isolation and characterization of mouse complementary DNAs encoding alpha and beta thyroid hormone receptors from thyrotrope cells: the mouse pituitary-specific beta 2 isoform differs at the amino terminus from the corresponding species from rat pituitary tumor cells. Wood, W.M., Ocran, K.W., Gordon, D.F., Ridgway, E.C. Mol. Endocrinol. (1991) [Pubmed]
  21. The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Kolterud, A., Alenius, M., Carlsson, L., Bohm, S. Development (2004) [Pubmed]
  22. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Ito, T., Udaka, N., Yazawa, T., Okudela, K., Hayashi, H., Sudo, T., Guillemot, F., Kageyama, R., Kitamura, H. Development (2000) [Pubmed]
  23. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Huang, H.P., Liu, M., El-Hodiri, H.M., Chu, K., Jamrich, M., Tsai, M.J. Mol. Cell. Biol. (2000) [Pubmed]
  24. Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose-mediated insulin secretion. Chu, K., Tsai, M.J. Diabetes (2005) [Pubmed]
  25. Transactivation of the mouse sulfonylurea receptor I gene by BETA2/NeuroD. Kim, J.W., Seghers, V., Cho, J.H., Kang, Y., Kim, S., Ryu, Y., Baek, K., Aguilar-Bryan, L., Lee, Y.D., Bryan, J., Suh-Kim, H. Mol. Endocrinol. (2002) [Pubmed]
  26. Laminar organization of the mouse dentate gyrus: insights from BETA2/Neuro D mutant mice. Del Turco, D., Gebhardt, C., Burbach, G.J., Pleasure, S.J., Lowenstein, D.H., Deller, T. J. Comp. Neurol. (2004) [Pubmed]
  27. Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus. Schwab, M.H., Bartholomae, A., Heimrich, B., Feldmeyer, D., Druffel-Augustin, S., Goebbels, S., Naya, F.J., Zhao, S., Frotscher, M., Tsai, M.J., Nave, K.A. J. Neurosci. (2000) [Pubmed]
  28. Glucose regulates insulin gene transcription by hyperacetylation of histone h4. Mosley, A.L., Ozcan, S. J. Biol. Chem. (2003) [Pubmed]
  29. CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6. Bohnsack, J.F. Blood (1992) [Pubmed]
  30. The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration. Tohyama, Y., Katagiri, K., Pardi, R., Lu, C., Springer, T.A., Kinashi, T. Mol. Biol. Cell (2003) [Pubmed]
  31. PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Kaneto, H., Nakatani, Y., Miyatsuka, T., Matsuoka, T.A., Matsuhisa, M., Hori, M., Yamasaki, Y. Diabetes (2005) [Pubmed]
  32. Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance. Gekeler, V., Boer, R., Uberall, F., Ise, W., Schubert, C., Utz, I., Hofmann, J., Sanders, K.H., Schächtele, C., Klemm, K., Grunicke, H. Br. J. Cancer (1996) [Pubmed]
  33. An effector role for platelets in systemic and local lipopolysaccharide-induced toxicity in mice, mediated by a CD11a- and CD54-dependent interaction with endothelium. Piguet, P.F., Vesin, C., Ryser, J.E., Senaldi, G., Grau, G.E., Tacchini-Cottier, F. Infect. Immun. (1993) [Pubmed]
  34. RACK1 binds to a signal transfer region of G betagamma and inhibits phospholipase C beta2 activation. Chen, S., Lin, F., Hamm, H.E. J. Biol. Chem. (2005) [Pubmed]
  35. Long-range interactions in neuronal gene expression: evidence from gene targeting in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster. Uusi-Oukari, M., Heikkilä, J., Sinkkonen, S.T., Mäkelä, R., Hauer, B., Homanics, G.E., Sieghart, W., Wisden, W., Korpi, E.R. Mol. Cell. Neurosci. (2000) [Pubmed]
  36. Identification of a functional NF-kappa B binding site in the murine T cell receptor beta 2 locus. Jamieson, C., Mauxion, F., Sen, R. J. Exp. Med. (1989) [Pubmed]
  37. TcR recognition of the MHC-peptide dimer: structural properties of a ternary complex. Vasmatzis, G., Cornette, J., Sezerman, U., DeLisi, C. J. Mol. Biol. (1996) [Pubmed]
  38. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins. Jacobs, R.L., Devlin, C., Tabas, I., Vance, D.E. J. Biol. Chem. (2004) [Pubmed]
  39. NeuroD2 is necessary for development and survival of central nervous system neurons. Olson, J.M., Asakura, A., Snider, L., Hawkes, R., Strand, A., Stoeck, J., Hallahan, A., Pritchard, J., Tapscott, S.J. Dev. Biol. (2001) [Pubmed]
  40. Inhibition of BETA2/NeuroD by Id2. Ghil, S.H., Jeon, Y.J., Suh-Kim, H. Exp. Mol. Med. (2002) [Pubmed]
  41. Quantitative analysis of expression of NeuroD, GAP43 and receptor tyrosine kinase B in developing mouse olfactory neuroepithelium. Yasui, R., Hasegawa, M., Doi, K., Shimizu, K., Ohtuski, N., Ishida, H., Nibu, K. Acta oto-laryngologica. Supplementum. (2004) [Pubmed]
  42. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Schwitzgebel, V.M., Scheel, D.W., Conners, J.R., Kalamaras, J., Lee, J.E., Anderson, D.J., Sussel, L., Johnson, J.D., German, M.S. Development (2000) [Pubmed]
  43. An attempt to generate neurons from an astrocyte progenitor cell line FBD-104. Horiuchi, M., Tomooka, Y. Neurosci. Res. (2005) [Pubmed]
  44. Expression in murine teratocarcinoma F9 cells of transcription factors involved in pancreas development. O'Driscoll, L., Gammell, P., Clynes, M. Transplant. Proc. (2004) [Pubmed]
  45. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Kojima, H., Fujimiya, M., Matsumura, K., Younan, P., Imaeda, H., Maeda, M., Chan, L. Nat. Med. (2003) [Pubmed]
  46. Molecular cloning and characterization of a cDNA encoding a novel basic helix-loop-helix protein structurally related to Neuro-D/BHF1. Yasunami, M., Suzuki, K., Maruyama, H., Kawakami, H., Nagai, Y., Hagiwara, M., Ohkubo, H. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  47. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Naya, F.J., Huang, H.P., Qiu, Y., Mutoh, H., DeMayo, F.J., Leiter, A.B., Tsai, M.J. Genes Dev. (1997) [Pubmed]
  48. NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. Breslin, M.B., Zhu, M., Lan, M.S. J. Biol. Chem. (2003) [Pubmed]
  49. Expression of NeuroD in the mouse taste buds. Suzuki, Y., Takeda, M., Obara, N. Cell Tissue Res. (2002) [Pubmed]
  50. Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Suzuki, Y., Mizoguchi, I., Nishiyama, H., Takeda, M., Obara, N. Chem. Senses (2003) [Pubmed]
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