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François Guillemot - One of the best experts on this subject based on the ideXlab platform.
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Neurogenin 2 regulates progenitor cell-cycle progression and Purkinje cell dendritogenesis in cerebellar development
Development (Cambridge England), 2012Co-Authors: Marta Florio, Ketty Leto, Luca Muzio, Andrea Tinterri, Aurora Badaloni, Laura Croci, Paola Zordan, Valeria Barili, Ilaria Albieri, François GuillemotAbstract:By serving as the sole output of the cerebellar cortex, integrating a myriad of afferent stimuli, Purkinje cells (PCs) constitute the principal neuron in cerebellar circuits. Several neurodegenerative cerebellar ataxias feature a selective cell-autonomous loss of PCs, warranting the development of regenerative strategies. To date, very little is known as to the regulatory cascades controlling PC development. During central nervous system development, the proneural gene Neurogenin 2 (Neurog2) contributes to many distinct neuronal types by specifying their fate and/or dictating development of their morphological features. By analyzing a mouse knock-in line expressing Cre recombinase under the control of Neurog2 cis-acting sequences we show that, in the cerebellar primordium, Neurog2 is expressed by cycling progenitors cell-autonomously fated to become PCs, even when transplanted heterochronically. During cerebellar development, Neurog2 is expressed in G1 phase by progenitors poised to exit the cell cycle. We demonstrate that, in the absence of Neurog2, both cell-cycle progression and neuronal output are significantly affected, leading to an overall reduction of the mature cerebellar volume. Although PC fate identity is correctly specified, the maturation of their dendritic arbor is severely affected in the absence of Neurog2, as null PCs develop stunted and poorly branched dendrites, a defect evident from the early stages of dendritogenesis. Thus, Neurog2 represents a key regulator of PC development and maturation.
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Post-translational modification of Ngn2 differentially affects transcription of distinct targets to regulate the balance between progenitor maintenance and differentiation
Development (Cambridge England), 2012Co-Authors: Christopher J. Hindley, François Guillemot, Fahad R. Ali, Gary S. Mcdowell, Alison Jones, Kevin Cheng, Anna PhilpottAbstract:Neurogenin 2 (Ngn2) controls neuronal differentiation cell-autonomously by transcriptional activation of targets such as NeuroD, while simultaneously controlling progenitor maintenance non-cell-autonomously by upregulating Delta expression and Notch signalling. Reduction in Cdk-dependent multisite phosphorylation of Ngn2 enhances its promoter binding affinity. This leads specifically to an increase in neuronal differentiation without an apparent increase in progenitor maintenance via Delta-Notch signalling, although the mechanism underlying this imbalance remains unclear. Here we show in Xenopus embryos and mouse P19 cells that the NeuroD promoter is substantially more sensitive to the phosphorylation status of Ngn2 than the Delta promoter, and that this can be attributed to differences in the ease of promoter activation. In addition, we also show that the phosphorylation status of Ngn2 regulates sensitivity to Notch signalling. These observations explain how Ngn2 post-translational modification in response to changes in the cell cycle kinase environment results in enhanced neuronal differentiation upon cell cycle lengthening.
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Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell cycling with differentiation during neurogenesis
Development (Cambridge England), 2011Co-Authors: Fahad R. Ali, François Guillemot, Christopher J. Hindley, Gary S. Mcdowell, Richard W. Deibler, Alison Jones, Marc W. Kirschner, Anna PhilpottAbstract:During development of the central nervous system, the transition from progenitor maintenance to differentiation is directly triggered by a lengthening of the cell cycle that occurs as development progresses. However, the mechanistic basis of this regulation is unknown. The proneural transcription factor Neurogenin 2 (Ngn2) acts as a master regulator of neuronal differentiation. Here, we demonstrate that Ngn2 is phosphorylated on multiple serine-proline sites in response to rising cyclin-dependent kinase (cdk) levels. This multi-site phosphorylation results in quantitative inhibition of the ability of Ngn2 to induce neurogenesis in vivo and in vitro. Mechanistically, multi-site phosphorylation inhibits binding of Ngn2 to E box DNA, and inhibition of DNA binding depends on the number of phosphorylation sites available, quantitatively controlling promoter occupancy in a rheostat-like manner. Neuronal differentiation driven by a mutant of Ngn2 that cannot be phosphorylated by cdks is no longer inhibited by elevated cdk kinase levels. Additionally, phosphomutant Ngn2-driven neuronal differentiation shows a reduced requirement for the presence of cdk inhibitors. From these results, we propose a model whereby multi-site cdk-dependent phosphorylation of Ngn2 interprets cdk levels to control neuronal differentiation in response to cell cycle lengthening during development.
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Neurogenin 2 has an essential role in development of the dentate gyrus.
Development (Cambridge England), 2008Co-Authors: Christophe Galichet, François Guillemot, Carlos ParrasAbstract:The dentate gyrus (DG) of the hippocampus has a central role in learning and memory in adult rodents. The DG is generated soon after birth, although new neurons continue to be generated in the DG throughout life. The proneural factors Mash1 (Ascl1) and Neurogenin 2 (Ngn2) are expressed during formation of the DG but their role in the development of this structure has not yet been addressed. Here, we show that Ngn2 is essential for the development of the DG. Ngn2 mutant mice have fewer DG progenitors and these cells present defects in neuronal differentiation. By contrast, the DG is normal in Mash1 mutant mice at birth, and loss of both Mash1 and Ngn2 does not aggravate the defect observed in Ngn2 single mutants. These data establish a unique role of Ngn2 in DG neurogenesis during development and raise the possibility that Ngn2 has a similar function in adult neurogenesis.
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Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells.
The European journal of neuroscience, 2007Co-Authors: Benedikt Berninger, François Guillemot, Magdalena GötzAbstract:In-vitro expanded neural stem cells (NSCs) of the adult subependymal zone (SEZ) may serve as a source for replacing degenerating neurones in disease and trauma. Crucial for the viability of this approach is the ability to selectively generate specific types of neurones from these cells. Here we show that NSCs derived from the adult mouse SEZ and expanded in vitro as neurosphere cells lose their in-vivo specification and generate a mixture of progeny comprising both GABAergic and also, surprisingly, glutamatergic neurones. When forced to express the pro-neural transcription factor Neurogenin 2, virtually all progeny of in-vitro expanded adult NSCs acquire a glutamatergic identity, whereas only GABAergic neurones are generated upon expression of the transcription factor Mash1. Respecification of expanded NSCs from the adult SEZ by Neurogenin 2 was accompanied by upregulation of the T-box transcription factor Tbr1, suggesting that their progeny had acquired a dorsal telencephalic identity. Thus, in-vitro expanded adult NSCs have the competence to become directed towards distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided.
Benedikt Berninger - One of the best experts on this subject based on the ideXlab platform.
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Cultured Subventricular Zone Progenitor Cells Transduced with Neurogenin-2 Become Mature Glutamatergic Neurons and Integrate into the Dentate Gyrus
PloS one, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+;
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cultured subventricular zone progenitor cells transduced with Neurogenin 2 become mature glutamatergic neurons and integrate into the dentate gyrus
PLOS ONE, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+). At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative). Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78%) expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.
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Reprogramming of postnatal astroglia of the mouse neocortex into functional, synapse-forming neurons.
Methods in molecular biology (Clifton N.J.), 2011Co-Authors: Christophe Heinrich, Magdalena Götz, Benedikt BerningerAbstract:Direct conversion of glia into neurons by cellular reprogramming represents a novel approach toward a cell-based therapy of neurodegenerative processes. Here we describe a protocol that allows for the direct and efficient in vitro reprogramming of mouse astroglia from the early postnatal neocortex by forced expression of single neurogenic fate determinants. By selective retrovirus-mediated expression of Neurogenin-2 (Neurog2) on the one hand, or the mouse homologue of Distal-less Dlx2 or the mammalian homologue of achaete-schute-1 (Mash1) on the other, it is possible to drive postnatal astroglia in culture toward the genesis of fully functional, synapse-forming, glutamatergic, i.e., excitatory, and GABAergic, i.e., inhibitory, neurons, respectively.
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Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex
Nature Protocols, 2011Co-Authors: Christophe Heinrich, Magdalena Götz, Alexandra Lepier, Timm Schroeder, Sergio Gascón, Giacomo Masserdotti, Rodrigo Sanchez, Tatiana Simon-ebert, Benedikt BerningerAbstract:Instructing glial cells to generate neurons may prove to be a strategy to replace neurons that have degenerated. Here, we describe a robust protocol for the efficient in vitro conversion of postnatal astroglia from the mouse cerebral cortex into functional, synapse-forming neurons. This protocol involves two steps: (i) expansion of astroglial cells (7 d) and (ii) astroglia-to-neuron conversion induced by persistent and strong retroviral expression of Neurog2 (encoding Neurogenin-2) or Mash1 (also referred to as achaete-scute complex homolog 1 or Ascl1 ) and/or distal-less homeobox 2 ( Dlx2 ) for generation of glutamatergic or GABAergic neurons, respectively (7–21 d for different degrees of maturity). Our protocol of astroglia-to-neuron conversion by a single neurogenic transcription factor provides a stringent experimental system to study the specification of a selective neuronal subtype, thus offering an alternative to the use of embryonic or neural stem cells. Moreover, it can be a useful model for studies of lineage conversion from non-neuronal cells, with potential for brain regenerative medicine.
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Neuronal Network Formation from Reprogrammed Early Postnatal Rat Cortical Glial Cells
Cerebral cortex (New York N.Y. : 1991), 2010Co-Authors: Robert Blum, Alexandra Lepier, Benedikt Berninger, Christophe Heinrich, Rodrigo Vega Sánchez, Eckart D. Gundelfinger, Magdalena GötzAbstract:In the subependymal zone and the dentate gyrus of the adult brain of rodents, neural stem cells with glial properties generate new neurons in a life-long process. The identification of glial progenitors outside the neurogenic niches, oligodendrocyte precursors in the healthy brain, and reactive astrocytes after cortical injury led to the idea of using these cells as endogenous cell source for neural repair in the cerebral cortex. Recently, our group showed that proliferating astroglia from the cerebral cortex can be reprogrammed into neurons capable of action potential firing by forced expression of neurogenic fate determinants but failed to develop synapses. Here, we describe a maturation profile of cultured reprogrammed NG2+ and glial fibrillary acidic protein+ glia cells of the postnatal rat cortex that ends with the establishment of a glutamatergic neuronal network. Within 3 weeks after viral expression of the transcription factor Neurogenin 2 (Ngn2), glia-derived neurons exhibit network-driven, glutamate receptor-dependent oscillations in Ca(2+) and exhibit functional pre- and postsynaptic specialization. Interestingly, the Ngn2-instructed glutamatergic network also supports the maturation of a γ-aminobutyric acid (GABA)ergic input via GABA(A) receptors in a non-cell autonomous manner. The "proof-of-principle" results imply that a single transcription factor may be sufficient to instruct a neuronal network from a glia-like cell source.
Joe Herbert - One of the best experts on this subject based on the ideXlab platform.
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Cultured Subventricular Zone Progenitor Cells Transduced with Neurogenin-2 Become Mature Glutamatergic Neurons and Integrate into the Dentate Gyrus
PloS one, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+;
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cultured subventricular zone progenitor cells transduced with Neurogenin 2 become mature glutamatergic neurons and integrate into the dentate gyrus
PLOS ONE, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+). At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative). Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78%) expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.
Alexandra Lepier - One of the best experts on this subject based on the ideXlab platform.
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Cultured Subventricular Zone Progenitor Cells Transduced with Neurogenin-2 Become Mature Glutamatergic Neurons and Integrate into the Dentate Gyrus
PloS one, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+;
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cultured subventricular zone progenitor cells transduced with Neurogenin 2 become mature glutamatergic neurons and integrate into the dentate gyrus
PLOS ONE, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+). At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative). Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78%) expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.
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Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex
Nature Protocols, 2011Co-Authors: Christophe Heinrich, Magdalena Götz, Alexandra Lepier, Timm Schroeder, Sergio Gascón, Giacomo Masserdotti, Rodrigo Sanchez, Tatiana Simon-ebert, Benedikt BerningerAbstract:Instructing glial cells to generate neurons may prove to be a strategy to replace neurons that have degenerated. Here, we describe a robust protocol for the efficient in vitro conversion of postnatal astroglia from the mouse cerebral cortex into functional, synapse-forming neurons. This protocol involves two steps: (i) expansion of astroglial cells (7 d) and (ii) astroglia-to-neuron conversion induced by persistent and strong retroviral expression of Neurog2 (encoding Neurogenin-2) or Mash1 (also referred to as achaete-scute complex homolog 1 or Ascl1 ) and/or distal-less homeobox 2 ( Dlx2 ) for generation of glutamatergic or GABAergic neurons, respectively (7–21 d for different degrees of maturity). Our protocol of astroglia-to-neuron conversion by a single neurogenic transcription factor provides a stringent experimental system to study the specification of a selective neuronal subtype, thus offering an alternative to the use of embryonic or neural stem cells. Moreover, it can be a useful model for studies of lineage conversion from non-neuronal cells, with potential for brain regenerative medicine.
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Neuronal Network Formation from Reprogrammed Early Postnatal Rat Cortical Glial Cells
Cerebral cortex (New York N.Y. : 1991), 2010Co-Authors: Robert Blum, Alexandra Lepier, Benedikt Berninger, Christophe Heinrich, Rodrigo Vega Sánchez, Eckart D. Gundelfinger, Magdalena GötzAbstract:In the subependymal zone and the dentate gyrus of the adult brain of rodents, neural stem cells with glial properties generate new neurons in a life-long process. The identification of glial progenitors outside the neurogenic niches, oligodendrocyte precursors in the healthy brain, and reactive astrocytes after cortical injury led to the idea of using these cells as endogenous cell source for neural repair in the cerebral cortex. Recently, our group showed that proliferating astroglia from the cerebral cortex can be reprogrammed into neurons capable of action potential firing by forced expression of neurogenic fate determinants but failed to develop synapses. Here, we describe a maturation profile of cultured reprogrammed NG2+ and glial fibrillary acidic protein+ glia cells of the postnatal rat cortex that ends with the establishment of a glutamatergic neuronal network. Within 3 weeks after viral expression of the transcription factor Neurogenin 2 (Ngn2), glia-derived neurons exhibit network-driven, glutamate receptor-dependent oscillations in Ca(2+) and exhibit functional pre- and postsynaptic specialization. Interestingly, the Ngn2-instructed glutamatergic network also supports the maturation of a γ-aminobutyric acid (GABA)ergic input via GABA(A) receptors in a non-cell autonomous manner. The "proof-of-principle" results imply that a single transcription factor may be sufficient to instruct a neuronal network from a glia-like cell source.
X Chen - One of the best experts on this subject based on the ideXlab platform.
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Cultured Subventricular Zone Progenitor Cells Transduced with Neurogenin-2 Become Mature Glutamatergic Neurons and Integrate into the Dentate Gyrus
PloS one, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+;
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cultured subventricular zone progenitor cells transduced with Neurogenin 2 become mature glutamatergic neurons and integrate into the dentate gyrus
PLOS ONE, 2012Co-Authors: X Chen, Alexandra Lepier, Benedikt Berninger, Abby Miriam Tolkovsky, Joe HerbertAbstract:We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG), but not undifferentiated neuronal progenitor cells (NPCs) from ventral subventricular zone (SVZ), results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2). NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control). By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+), whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+). At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative). Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78%) expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.