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Gene Review

neurog1  -  neurogenin 1

Danio rerio

Synonyms: NGN-1, NeuroD3, Neurogenic differentiation factor 3, Neurogenin-1, Neurogenin-related protein 1, ...
 
 
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Disease relevance of neurog1

  • In addition, ngn1 is expressed in a subset of cells within the otic vesicle that will delaminate to form the octaval (statoacoustic) ganglion [1].
 

High impact information on neurog1

  • Here we show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish [2].
  • Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the pan-neuronal marker Hu in nonneural ectoderm [2].
  • In the zebrafish, the transcription factor neurogenin 1 is essential for the generation of the sensory ganglion from the placode, but is dispensable for the migration of the primordium and the initial development of neuromasts [3].
  • In all territories, the her3 transcription domain encompasses regions in which neurogenin 1 (neurog1) is not transcribed, suggesting regulatory interactions between the two genes [4].
  • Gel retardation assays suggest that the repression of neurog1 transcription occurs by binding of Her3 to specific DNA sequences in the neurog1 promoter [4].
 

Biological context of neurog1

  • Blocking Hh pathway activation at later stages of embryogenesis with the steroidal alkaloid, cyclopamine, further reveals that the requirement for a Hh signal response in DRG precursors correlates with the onset of ngn1 expression [5].
  • A ngn1 transgene faithfully responds to Her5 and deletion analysis of the transgene identifies an E-box in a ngn1 upstream enhancer to be required for repression by Her5 [6].
 

Anatomical context of neurog1

  • Delta/Notch signaling is required for neural crest formation. ngn1 is expressed in primary neurons; inhibiting Ngn1 activity prevents Rohon-Beard cell formation but not formation of other primary neurons [7].
  • Furthermore, different cell populations show different requirements for ash1a and ngn1 within the epiphysis [8].
  • Lateral line sensory neuromasts develop independently of ngn1 function, suggesting that two derivatives of lateral line placodes, ganglia and migrating primordia, are under separate genetic control [1].
  • Gene knockdown experiments demonstrate that loss of function of either gene, but not of the related proneural gene neurogenin1 (ngn1), abrogate the appearance of hair cell markers [9].
  • Interfering with ngn1 function using a specific antisense morpholino oligonucleotide blocks differentiation of all cranial ganglia but not associated glial cells [1].
 

Associations of neurog1 with chemical compounds

  • The number of GFP-expressing cells measured by flow cytometry decreased, and expression of neurogenin-1, a downstream target of the shh signaling pathway, was down-regulated, providing additional supporting data on the effects of cadmium on shh [10].
 

Regulatory relationships of neurog1

 

Other interactions of neurog1

  • The earliest nrd-positive cells in the brain and the trunk are a subset of the primary neurons. ngn1 is not expressed in the eye [12].
  • Activation of notch1 leads to strong activation of her4, to suppression of neurogenin transcription and, ultimately, to a reduction in the number of primary neurons [13].
  • We show that ash1a and ngn1 function in parallel redundant pathways to regulate neurogenesis downstream of flh [8].
  • The expression of zebrafish neurogenin precedes and overlaps that of HuC, one of the earliest neuronal precursor markers [11].
  • This study suggests that zath3 and ngn1 have partially overlapping roles in early neurogenesis [14].

References

  1. Neurogenin1 defines zebrafish cranial sensory ganglia precursors. Andermann, P., Ungos, J., Raible, D.W. Dev. Biol. (2002) [Pubmed]
  2. Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl. Jeong, J.Y., Einhorn, Z., Mercurio, S., Lee, S., Lau, B., Mione, M., Wilson, S.W., Guo, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Supernumerary neuromasts in the posterior lateral line of zebrafish lacking peripheral glia. López-Schier, H., Hudspeth, A.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling. Hans, S., Scheer, N., Riedl, I., v Weizsäcker, E., Blader, P., Campos-Ortega, J.A. Development (2004) [Pubmed]
  5. Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons. Ungos, J.M., Karlstrom, R.O., Raible, D.W. Development (2003) [Pubmed]
  6. Her5 acts as a prepattern factor that blocks neurogenin1 and coe2 expression upstream of Notch to inhibit neurogenesis at the midbrain-hindbrain boundary. Geling, A., Plessy, C., Rastegar, S., Strähle, U., Bally-Cuif, L. Development (2004) [Pubmed]
  7. Delta/Notch signaling promotes formation of zebrafish neural crest by repressing Neurogenin 1 function. Cornell, R.A., Eisen, J.S. Development (2002) [Pubmed]
  8. Ash1a and Neurogenin1 function downstream of Floating head to regulate epiphysial neurogenesis. Cau, E., Wilson, S.W. Development (2003) [Pubmed]
  9. Proneural gene requirement for hair cell differentiation in the zebrafish lateral line. Sarrazin, A.F., Villablanca, E.J., Nuñez, V.A., Sandoval, P.C., Ghysen, A., Allende, M.L. Dev. Biol. (2006) [Pubmed]
  10. Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) embryos. Yu, R.M., Lin, C.C., Chan, P.K., Chow, E.S., Murphy, M.B., Chan, B.P., Müller, F., Strähle, U., Cheng, S.H. Toxicol. Sci. (2006) [Pubmed]
  11. Overexpression of neurogenin induces ectopic expression of HuC in zebrafish. Kim, C.H., Bae, Y.K., Yamanaka, Y., Yamashita, S., Shimizu, T., Fujii, R., Park, H.C., Yeo, S.Y., Huh, T.L., Hibi, M., Hirano, T. Neurosci. Lett. (1997) [Pubmed]
  12. Expression of zebrafish bHLH genes ngn1 and nrd defines distinct stages of neural differentiation. Korzh, V., Sleptsova, I., Liao, J., He, J., Gong, Z. Dev. Dyn. (1998) [Pubmed]
  13. her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling. Takke, C., Dornseifer, P., v Weizsäcker, E., Campos-Ortega, J.A. Development (1999) [Pubmed]
  14. Zath3, a neural basic helix-loop-helix gene, regulates early neurogenesis in the zebrafish. Park, S.H., Yeo, S.Y., Yoo, K.W., Hong, S.K., Lee, S., Rhee, M., Chitnis, A.B., Kim, C.H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
 
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