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Neurogenin 2 (Gene NEUROG2) Homo SapiensThe NEUROG2 (map locus: 4q25) gene product, NGN2/Neurogenin 2, is a 272 AA (28.6 kDa) basic helix-loop-helix (bHLH) transcription factor with a 56 AA helix-loop-helix (HLH) motif (110 to 165) and a HLH internal DNA-binding 12 AA basic motif (122-133). The phosphorylation of Ser231 and S234 has recently been linked to the interaction of Ngn2 with LIM homeodomain transcription factors and the regulation of neural cell-type specification, Ma YC, et al. (2008). BasicHLH transcription factors are heterodimeric. Neural basic helix-loop-helix (bHLH) transcription factors are cell intrinsic factors that control commitment to neuronal lineage, play an important role in neuronal cell type specification and neural architecture. Ngn1 and Ngn2 are expressed in the developing neocortex where they help regulated corticogenesis. They regulate germinal zone genes including cortical plate and subplate factors, Mattar P, et al. (2004). Ngn2 regulates the development of specific sensory neurons. Sensory neurons that form cranial sensory ganglia of vertebrates are derived from neurogenic placodes by genetic mechanisms that depend upon neurogenin family members, wherein one family member is typically expressed in each placode type, Furlong RF, and Graham A. (2005). Ngn2 positive populations of premigratory neural crest cells (NCC) are biased towards sensory ganglia; whereas in dorsal root ganglia they are equally disposed to generate neurons or glia, Zirlinger M, et al. (2002). Ngn2 is a determination factor for epibranchial placode-derived sensory neurons, Fode C, et al. (1998) and an initial wave regulator of sensory neuron differentiation in dorsal root ganglia (DRG), Ota M and Ito K. (2006), Ma Q, et al (1999). Ngn2 regulates neural structure, in part, by controlling cell migration. It helps to maintain the dorsal and ventral domains of the telencephalon by inhibiting dorsal (cortex) to ventral (ganglionic eminence (GE)) cell migration, Chapouton P, et al. (2001). The small GTP-binding protein Rho family GTPase 2 (Rnd2) has recently been shown to be an essential regulator of radial migration of cortical neurons in the cerebral cortex under the direct control of Ngn2, Heng JI, et al. (2008). The decision between maintenance and division of neural stem cells and progression to postmitotic differentiated neurons or glial cells is controlled by the balance of bHLH activator-type (neurogenins, Mash1, Math) and repressor-type (Hes1, Hes3, Hes5) factors, Kageyama R, et al. (2005). This type of regulation is manifest in the development of the choroids plexus, a non-neural secretory brain tissue. Ngn2 enhances the formation of Cajal-Retzius cells, specialized neurons that guide neuronal migration in the dorsal telencephalic midline region). Conversely, Hes genes antagonize Ngn2 and promote specification of choroids plexus epithelial cells, Imayoshi I, et al. (2008). Future interest in Ngn2 is likely to be promoted because of its potential contributions to an understanding of Parkinson’s disease and possible therapies. Andersson E, et al. (2006) and Kele J, et al. (2006) reported that Ngn2 is essential for the differentiation of Nurr1+ postmitotic mesencephalic dopaminergic (mesDA) neurons within the ventricular zone of the ventral midline. Andersson EK et al. (2007) have demonstrated that the generation of morphologically mature (via marker analysis) TH-expressing midbrain dopaminergic neurons (mesDA) from expanded neural progenitor cells requires both Nurr1 and Ngn2 expression. Sigma offers antibodies and shRNAs useful for the study of NEUROG2 (NGN2)gene products. References: Andersson EK, et al. (2007) Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells. Exp Cell Res. 313: 1172-1180. |
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