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Gene Review

Neurog2  -  neurogenin 2

Mus musculus

Synonyms: Ath4a, Atoh4, Helix-loop-helix protein mATH-4A, Math4A, NGN-2, ...
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Disease relevance of Neurog2

  • Molecular and cellular analysis of the cortico-striatal boundary revealed that neurogenin 2 regulates the fasciculation of the cortico-striatal boundary which may explain the non cell-autonomous nature of the migration defect as detected by in vitro transplantation [1].

High impact information on Neurog2

  • Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells [2].
  • This blockade is counteracted by Ngn2, which accumulates heterogeneously in pMN cells, thereby releasing a subset of the progenitors to differentiate and activate expression of post-mitotic motor neuron genes [2].
  • In contrast, misexpression of Ngn2 in Mash1-expressing progenitors does not result in any overt change in neuronal phenotype [3].
  • The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of neural progenitors in the central and peripheral nervous systems [3].
  • Neurogenin1 (Ngn1), Neurogenin2 (Ngn2), and Mash1 encode bHLH transcription factors with neuronal determination functions [4].

Biological context of Neurog2

  • The mutant epibranchial progenitor cells fail to express Neurog2 that is required for the determination of neuronal precursors, and other basic helix-loop-helix as well as the paired homeobox Phox2 genes that are essential for neural differentiation and maintenance [5].
  • Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype [6].
  • MATH4A-E12 heterodimers, but not MATH4A-MASH1, bind to a consensus E-box sequence [7].
  • Here, we demonstrate that expression of the proneural gene Neurogenin2 (Ngn2) in the ventral spinal cord results from the modular activity of three enhancers active in distinct progenitor domains, suggesting that Ngn2 expression is controlled by dorsoventral patterning signals [8].
  • The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function [9].

Anatomical context of Neurog2


Associations of Neurog2 with chemical compounds

  • In contrast, simultaneous transfection of Ngn2 and HB9 cDNA increased the expression of Isl1/2, a motoneuron marker, when the cells were maintained in medium supplemented with retinoic acid, forskolin, and sonic hedgehog [14].
  • By crossing neurogenin 2 (Ngn2-CreER) with Cre-reporter mice expressing YFP or GFP reporter genes, it was possible to observe living cells after treating slice cultures with 4-hydroxytamoxifen to induce Cre recombinase activation [15].

Physical interactions of Neurog2

  • Interaction assays in yeast and in vitro demonstrate that MATH4A interacts efficiently with both MASH1 and the ubiquitous bHLH protein E12 [7].

Regulatory relationships of Neurog2

  • Pax6 promotes neuronal differentiation via transcriptional regulation of the Neurogenin2 (Ngn2) gene, although Pax6 expression appears in proliferating neuroepithelial cells before the onset of neurogenesis [16].
  • Furthermore, a population of Olig2-expressing NSFCs also expressed Ngn2 [14].
  • These defects are due to a failure of neurogenesis and apoptosis, a defect that can be rescued by ectopic Ngn2 under the control of the Mash1 promoter [17].
  • Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain [18].

Other interactions of Neurog2

  • Although Mash1 normally has no detectable function in dopaminergic neuron development, it could partially rescue the generation of dopaminergic neuron precursors in the absence of Ngn2 [10].
  • This was accompanied with an expansion of dorsal identities ventrally as shown by the expanded expression domains of pallial markers Pax6 and Ngn2 [19].
  • In their place, the dorsal regulators, Pax6, neurogenin 1 and neurogenin 2 are found ectopically [20].
  • The antagonistic relationship between Ngn2 and Olig2 is mediated by protein interactions that squelch activity as well as competition for shared DNA-binding sites [2].
  • To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification [21].


  1. The transcription factor neurogenin 2 restricts cell migration from the cortex to the striatum. Chapouton, P., Schuurmans, C., Guillemot, F., Götz, M. Development (2001) [Pubmed]
  2. Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells. Lee, S.K., Lee, B., Ruiz, E.C., Pfaff, S.L. Genes Dev. (2005) [Pubmed]
  3. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Parras, C.M., Schuurmans, C., Scardigli, R., Kim, J., Anderson, D.J., Guillemot, F. Genes Dev. (2002) [Pubmed]
  4. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Fode, C., Ma, Q., Casarosa, S., Ang, S.L., Anderson, D.J., Guillemot, F. Genes Dev. (2000) [Pubmed]
  5. Eya1 and Six1 are essential for early steps of sensory neurogenesis in mammalian cranial placodes. Zou, D., Silvius, D., Fritzsch, B., Xu, P.X. Development (2004) [Pubmed]
  6. Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. Schuurmans, C., Armant, O., Nieto, M., Stenman, J.M., Britz, O., Klenin, N., Brown, C., Langevin, L.M., Seibt, J., Tang, H., Cunningham, J.M., Dyck, R., Walsh, C., Campbell, K., Polleux, F., Guillemot, F. EMBO J. (2004) [Pubmed]
  7. Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors. Gradwohl, G., Fode, C., Guillemot, F. Dev. Biol. (1996) [Pubmed]
  8. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Scardigli, R., Schuurmans, C., Gradwohl, G., Guillemot, F. Neuron (2001) [Pubmed]
  9. Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex. Hand, R., Bortone, D., Mattar, P., Nguyen, L., Heng, J.I., Guerrier, S., Boutt, E., Peters, E., Barnes, A.P., Parras, C., Schuurmans, C., Guillemot, F., Polleux, F. Neuron (2005) [Pubmed]
  10. Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Kele, J., Simplicio, N., Ferri, A.L., Mira, H., Guillemot, F., Arenas, E., Ang, S.L. Development (2006) [Pubmed]
  11. The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons. Marmigère, F., Montelius, A., Wegner, M., Groner, Y., Reichardt, L.F., Ernfors, P. Nat. Neurosci. (2006) [Pubmed]
  12. Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Helms, A.W., Battiste, J., Henke, R.M., Nakada, Y., Simplicio, N., Guillemot, F., Johnson, J.E. Development (2005) [Pubmed]
  13. A screen for downstream effectors of Neurogenin2 in the embryonic neocortex. Mattar, P., Britz, O., Johannes, C., Nieto, M., Ma, L., Rebeyka, A., Klenin, N., Polleux, F., Guillemot, F., Schuurmans, C. Dev. Biol. (2004) [Pubmed]
  14. Role of transcription factors in motoneuron differentiation of adult human olfactory neuroepithelial-derived progenitors. Zhang, X., Cai, J., Klueber, K.M., Guo, Z., Lu, C., Winstead, W.I., Qiu, M., Roisen, F.J. Stem Cells (2006) [Pubmed]
  15. Conditional labeling of newborn granule cells to visualize their integration into established circuits in hippocampal slice cultures. Raineteau, O., Hugel, S., Ozen, I., Rietschin, L., Sigrist, M., Arber, S., Gähwiler, B.H. Mol. Cell. Neurosci. (2006) [Pubmed]
  16. Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex. Arai, Y., Funatsu, N., Numayama-Tsuruta, K., Nomura, T., Nakamura, S., Osumi, N. J. Neurosci. (2005) [Pubmed]
  17. Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells. McNay, D.E., Pelling, M., Claxton, S., Guillemot, F., Ang, S.L. Mol. Endocrinol. (2006) [Pubmed]
  18. Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Andersson, E., Jensen, J.B., Parmar, M., Guillemot, F., Björklund, A. Development (2006) [Pubmed]
  19. Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Backman, M., Machon, O., Mygland, L., van den Bout, C.J., Zhong, W., Taketo, M.M., Krauss, S. Dev. Biol. (2005) [Pubmed]
  20. Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Toresson, H., Potter, S.S., Campbell, K. Development (2000) [Pubmed]
  21. Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Lee, S.K., Pfaff, S.L. Neuron (2003) [Pubmed]
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