Neurogenin-2 is a member of the neurogenin subfamily of basic helix-loop-helix (bHLH) transcription factor genes that play an important role in neurogenesis from migratory neural crest cells (Simmons et al., 2001; Yan et al., 2001).

Sommer et al. (1996) determined that the mouse Ngn2 gene contains a single coding exon.

During mouse neurogenesis, Ngn2 and Ngn1 (NEUROG1; 601726) are expressed in distinct progenitor populations in the central and peripheral nervous systems (Sommer et al., 1996; Ma et al., 1996). Their expression patterns partially overlap in some areas but are distinct in others. Targeted mutation analyses showed that Ngn1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia (Ma et al., 1998) and that Ngn2 is essential for the determination of precursors for epibranchial placode-derived sensory neurons (Fode et al., 1998).

Yan et al. (2001) observed that in the developing chick retina, Ngn2 was expressed in a subpopulation of proliferating progenitor cells. Ectopic expression of Ngn2 in nonneural, retinal pigment epithelial cell culture triggered de novo generation of cells that expressed neural-specific markers and exhibited neuronal morphologies. Further molecular and morphologic analyses showed that the main products of the induced neurogenesis were cells resembling young photoreceptor cells and cells resembling retinal ganglion cells. The generation of multiple cell types suggested that Ngn2 induces various retinal pathways. Thus, whereas Ngn2 in the peripheral nervous system specifies one type of sensory neuron, Ngn2 in the retina is likely to be involved in a common step leading to different cellular pathways. The finding that Ngn2 can instruct nonneuronal retinal pigment epithelial cells to differentiate toward retinal neurons demonstrated one possible way to induce de novo retinal neurogenesis.

Ma et al. (1999) presented a detailed analysis of mouse Ngn1, also called Neurod3, and Neurog2 expression during neural crest migration and early dorsal root gangliogenesis in wildtype and neurogenin-deficient mouse embryos. They concluded that Neurod3 and Neurog2 control 2 distinct phases of neurogenesis that generate different classes of sensory neurons.

Using assays in transgenic mice, Simmons et al. (2001) identified separable regulatory elements both 5-prime and 3-prime of the mouse Neurog2 coding region that direct Neurog2 expression to distinct but partially overlapping neural progenitor cell populations within the developing spinal cord. Analysis of reporter gene expression in the transgenic mice led the authors to conclude that Neurog2 progenitor cells in the ventral domain give rise to a subset of motor neurons, while Neurog2 progenitor cells in the dorsal domain give rise to a subset of interneurons that send their axons to the floor plate.

From study of reporter gene constructs in transgenic mice, Scardigli et al. (2001) found that expression of Neurog2 in the ventral spinal cord results from the modular activity of at least 3 enhancers that are active in distinct progenitor domains. They observed that Neurog2-deficient embryos displayed striking defects in ventral spinal cord gene expression, and concluded that Neurog2 function is required for the correct expression of Pax6 (607108) and several homeodomain proteins normally expressed in defined neuronal populations. By examining Neurog2 expression and enhancer activity in Pax6 mutant mice, Scardigli et al. (2001) concluded that Pax6 regulates Neurog2 expression in the spinal cord by controlling distinct enhancer elements that are active at different positions along the dorsoventral axis. They hypothesized that Neurog2 is both responsive to and a regulator of genetic pathways that provide positional identity and specify neuronal fates in the ventral spinal cord.

Using embryonic chicken and rodent models, Mizuguchi et al. (2001), Novitch et al. (2001), and Zhou et al. (2001) found that Olig2 (606386) and Ngn2 were coexpressed in motoneuron progenitors and that both were required for motoneuron differentiation.

Lee and Pfaff (2003) showed that Neurod4 (611635) and Ngn2 actively participated with Isl1 (600366) and Lhx3 (600577) to specify motor neuron subtype in embryonic chicken spinal cord and in P19 mouse stem cells.

Heng et al. (2008) demonstrated that the proneural protein Neurog2, which controls neurogenesis in the embryonic cortex, directly induces the expression of the small GTP-binding protein Rnd2 (601555) in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2-mutant neurons is sufficient to rescue their ability to migrate. Heng et al. (2008) concluded that their results identified Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrated that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behavior of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP-binding protein.