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Gene Review

NEUROG2  -  neurogenin 2

Homo sapiens

Synonyms: ATOH4, Atoh4, BHLHA8, Class A basic helix-loop-helix protein 8, Math4A, ...
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Disease relevance of NEUROG2

  • In the developing retina, the production of ganglion cells is dependent on the proneural proteins NGN2 and ATH5, whose activities define stages along the pathway converting progenitors into newborn neurons [1].

High impact information on NEUROG2

  • In the developing neural tube, combinatorial interactions between the proneural transcription factor Ngn2 and the basic helix-loop-helix transcription factor Olig2 specify the formation of motor neurons or oligodendrocytes [2].
  • The selected cells are those in which the upregulation of NGN2, the downregulation of HES1 and the autostimulation of ATH5 are coordinated with the progression of progenitors through the last cell cycle [1].
  • Mash1, but not Ngn2, spatially and temporally colocalized with aldehyde dehydrogenase 2 (AHD2), a specific midbrain DA neuronal progenitor marker, in the early embryonic ventral mesencephalon [3].
  • Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells [4].
  • We over-expressed Ngn2 and Nurr1, two genes present in the ventral midbrain and important for normal development of mesDA neurons, in multi-passaged neurosphere-expanded midbrain progenitors [4].

Biological context of NEUROG2

  • Whereas Ngn2 inhibited cell division and the production of neurons even in the presence of mitogens, Mash1 allowed the progenitors to divide while retaining neurogenic potential [5].
  • 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 [6].
  • Gene expression analysis showed that ngn2 did not induce ath5, and ath5 did not induce ngn2, but both induced neuroD and RaxL [7].

Anatomical context of NEUROG2

  • The basic helix-loop-helix transcription factor Neurogenin2 (NGN2) is expressed in distinct populations of neural progenitor cells within the developing central and peripheral nervous systems [8].
  • Persistent -gal activity revealed that the NGN2 progenitor cells in the dorsal domain give rise to a subset of interneurons that send their axons to the floor plate, and the NGN2 progenitors in the ventral domain give rise to a subset of motor neurons [8].
  • Here we provide evidence that cycling neuroepithelial cells pass through a neurogenic state in which they are situated apically, as defined by the capacity to express Notch1, Delta1, and Neurogenin2 (Ngn2) [9].
  • Photoreceptor genesis appears to employ two transcriptional pathways: ngn2-->neuroD-->raxL and ath5-->neuroD-->raxL. ngn2 and ath5 function in progenitors, which can potentially develop into different cell types. neuroD represents one of the central steps in photoreceptor specification [10].

Other interactions of NEUROG2

  • An interesting feature of this expression, however, is that the expression patterns vary amongst the vertebrates; for example, mammals and fish express ngn-1 in the ophthalmic trigeminal placode where birds use ngn-2 [11].


  1. A bHLH transcriptional network regulating the specification of retinal ganglion cells. Matter-Sadzinski, L., Puzianowska-Kuznicka, M., Hernandez, J., Ballivet, M., Matter, J.M. Development (2005) [Pubmed]
  2. Molecular mechanisms controlling cortical gliogenesis. Sauvageot, C.M., Stiles, C.D. Curr. Opin. Neurobiol. (2002) [Pubmed]
  3. Differential actions of the proneural genes encoding Mash1 and neurogenins in Nurr1-induced dopamine neuron differentiation. Park, C.H., Kang, J.S., Kim, J.S., Chung, S., Koh, J.Y., Yoon, E.H., Jo, A.Y., Chang, M.Y., Koh, H.C., Hwang, S., Suh-Kim, H., Lee, Y.S., Kim, K.S., Lee, S.H. J. Cell. Sci. (2006) [Pubmed]
  4. Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells. Andersson, E.K., Irvin, D.K., Ahlsiö, J., Parmar, M. Exp. Cell Res. (2007) [Pubmed]
  5. Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1. Kim, H.J., Sugimori, M., Nakafuku, M., Svendsen, C.N. Exp. Neurol. (2007) [Pubmed]
  6. 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]
  7. A role of ath5 in inducing neuroD and the photoreceptor pathway. Ma, W., Yan, R.T., Xie, W., Wang, S.Z. J. Neurosci. (2004) [Pubmed]
  8. Neurogenin2 expression in ventral and dorsal spinal neural tube progenitor cells is regulated by distinct enhancers. Simmons, A.D., Horton, S., Abney, A.L., Johnson , J.E. Dev. Biol. (2001) [Pubmed]
  9. Interkinetic nuclear movement may provide spatial clues to the regulation of neurogenesis. Murciano, A., Zamora, J., López-Sánchez, J., Frade, J.M. Mol. Cell. Neurosci. (2002) [Pubmed]
  10. bHLH genes and retinal cell fate specification. Yan, R.T., Ma, W., Liang, L., Wang, S.Z. Mol. Neurobiol. (2005) [Pubmed]
  11. Vertebrate neurogenin evolution: long-term maintenance of redundant duplicates. Furlong, R.F., Graham, A. Dev. Genes Evol. (2005) [Pubmed]
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