Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms.

By Yi Sun, M. Nadal-Vicens, Stephanie Misono, Michael Z. Lin, A. Zubiaga, X. Hua, G. Fan, Michael E. Greenberg. Cell, 2001

822 citations recorded by the source corpus.

The mechanisms by which neural stem cells give rise to neurons, astrocytes, or oligodendrocytes are beginning to be elucidated. However, it is not known how the specification of one cell lineage results in the suppression of alternative fates. We find that in addition to inducing neurogenesis, the bHLH transcription factor neurogenin (Ngn1) inhibits the differentiation of neural stem cells into astrocytes. While Ngn1 promotes neurogenesis by functioning as a transcriptional activator, Ngn1 inhibits astrocyte differentiation by sequestering the CBP-Smad1 transcription complex away from astrocyte differentiation genes, and by inhibiting the activation of STAT transcription factors that are necessary for gliogenesis. Thus, two distinct mechanisms are involved in the activation and suppression of gene expression during cell-fate specification by neurogenin.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/03b9d1f93f70174fc83690ddd8992cc7b2e8d9c7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. B. Barres
2. D. Rowitch
3. Ryoichiro Kageyama
4. M. Götz
5. G. Fishell
6. J. Frisén
7. Peng Jin
8. T. Ohtsuka

In Developmental Neuroscience

1. Ryoichiro Kageyama
2. T. Ohtsuka
3. B. Barres
4. M. Götz
5. P. Malatesta
6. D. Rowitch
7. N. Gaiano
8. Diogo S. Castro

In Molecular Biology

1. J. Massagué
2. J. Seoane
3. Ryoichiro Kageyama
4. T. Ohtsuka
5. D. Wotton
6. M. Götz
7. P. Malatesta
8. N. Gaiano

Citations in the corpus

• Astrocytes and disease: a neurodevelopmental perspective. (2012, background): “Thus, the data would seem to favor a role for proneural factors like neurogenins in inhibiting gliogenesis, in the case of Ngn1, by sequestering the CBP/p300/Smad1 complex away from glial-specific promoters (Sun et al. 2001).”
• [P2.15]: Oscillations in notch signaling regulate maintenance of neural progenitors (2008, neutral): “Apparently, Ngn2 oscillation cannot induce neuronal differentiation, although Ngn2 is known to have a neurogenic activity (Ma et al., 1996; Nieto et al., 2001; Sun et al., 2001).”
• The role of notch in promoting glial and neural stem cell fates. (2002, background): “Although this in vivo work did not address whether Notch acted instructively to specify astrocyte identity, a recent in vitro study has suggested that Notch can “instructively restrict” CNS stem cells to become astrocytes (Tanigaki et al. 2001).”
• Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, background): “Neurog1 is a transcription factor expressed only at the early stage of differentiation, and it promotes neuronal differentiation while inhibiting astrocyte differentiation [28,29].”
• BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. (2003, neutral): “Two others, junB and inin neuroepithelial cells (Nakashima et al., 1999; Sun et al., 2001).”
• The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. (2001, neutral): “2 together promote oligodendrocyte neuronal differentiation (Sun et al., 2001).”
• Proneural genes and the specification of neural cell types (2002, background): “A recent study has proposed an unexpected mechanism to account for the inhibition by Ngn1 of astrocytic differentiation in the cerebral corte”
• The Hes gene family: repressors and oscillators that orchestrate embryogenesis (2007, background): “…such as neurogenin 1 (Ngn1, also known as Neurog1 – Mouse Genome Informatics) have dual activities: they not only activate neuronal-specific gene expression, but they also inhibit astrocyte-specific gene expression by sequestering coactivators of these genes, such as p300 (Sun et al., 2001).”
• Embryo-derived stem cells: of mice and men. (2001, background): “1999), and a recent report suggests a possible interaction with neurogenic bHLH proteins (Sun et al. 2001).”
• Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome (2005, background): “Neurogenins inhibit gliogenesis by sequestering CBP-Smad1 away from astrocyte differentiation genes and by blocking activation of STAT1/3 (ref”
• Glial cells generate neurons: the role of the transcription factor Pax6 (2002, background): “Pax6 influences bHLH transcription factors The prominent neurogenic effect of Pax6 raises the question how Pax6 interacts with transcription factors of the bHLH family that have important roles in neurogenesi”
• A Novel Secretory Factor, Neurogenesin-1, Provides Neurogenic Environmental Cues for Neural Stem Cells in the Adult Hippocampus (2003, neutral): “These bHLH transcription factors include neurogenin1 and 2, Mash1, and Math1 (Guillemot et al., 1993; Ma et al., 1996; Ben-Arie et al., 1997; Fode et al., 1998; Sun et al., 2001).”