Abstract
The transcription factor ATF5 is expressed in cells of the embryonic and neonatal ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for their differentiation into neurons and astrocytes. Here, we show that ATF5 plays a major role in directing oligodendrocyte development. ATF5 is expressed by oligodendrocyte precursors but is absent from mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4 + oligodendrocyte precursors in cycle and inhibits their differentiation into oligodendrocytes in vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a dominant-negative form of the protein) accelerates oligodendrocyte differentiation of O4+ cells in vitro and of SVZ cells in vivo. Significantly, the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo results in aberrant migration. Thus, appropriately regulated expression of ATF5 is required for proper expansion of oligodendroglial progenitors as well as for their timely differentiation. Regulation of oligodendrocyte, astrocyte, and neuronal differentiation indicates that ATF5 operates as a general regulator of the timing of differentiation, independent of cell lineage.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 372-380 |
| Number of pages | 9 |
| Journal | Molecular and Cellular Neuroscience |
| Volume | 29 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Developmental Neuroscience
Cite this
ATF5 regulates the proliferation and differentiation of oligodendrocytes. / Mason, Jeffrey L.; Angelastro, James M; Ignatova, Tatyana N.; Kukekov, Valery G.; Lin, Grace; Greene, Lloyd A.; Goldman, James E.
In: Molecular and Cellular Neuroscience, Vol. 29, No. 3, 07.2005, p. 372-380.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ATF5 regulates the proliferation and differentiation of oligodendrocytes
AU - Mason, Jeffrey L.
AU - Angelastro, James M
AU - Ignatova, Tatyana N.
AU - Kukekov, Valery G.
AU - Lin, Grace
AU - Greene, Lloyd A.
AU - Goldman, James E.
PY - 2005/7
Y1 - 2005/7
N2 - The transcription factor ATF5 is expressed in cells of the embryonic and neonatal ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for their differentiation into neurons and astrocytes. Here, we show that ATF5 plays a major role in directing oligodendrocyte development. ATF5 is expressed by oligodendrocyte precursors but is absent from mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4 + oligodendrocyte precursors in cycle and inhibits their differentiation into oligodendrocytes in vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a dominant-negative form of the protein) accelerates oligodendrocyte differentiation of O4+ cells in vitro and of SVZ cells in vivo. Significantly, the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo results in aberrant migration. Thus, appropriately regulated expression of ATF5 is required for proper expansion of oligodendroglial progenitors as well as for their timely differentiation. Regulation of oligodendrocyte, astrocyte, and neuronal differentiation indicates that ATF5 operates as a general regulator of the timing of differentiation, independent of cell lineage.
AB - The transcription factor ATF5 is expressed in cells of the embryonic and neonatal ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for their differentiation into neurons and astrocytes. Here, we show that ATF5 plays a major role in directing oligodendrocyte development. ATF5 is expressed by oligodendrocyte precursors but is absent from mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4 + oligodendrocyte precursors in cycle and inhibits their differentiation into oligodendrocytes in vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a dominant-negative form of the protein) accelerates oligodendrocyte differentiation of O4+ cells in vitro and of SVZ cells in vivo. Significantly, the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo results in aberrant migration. Thus, appropriately regulated expression of ATF5 is required for proper expansion of oligodendroglial progenitors as well as for their timely differentiation. Regulation of oligodendrocyte, astrocyte, and neuronal differentiation indicates that ATF5 operates as a general regulator of the timing of differentiation, independent of cell lineage.
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UR - http://www.scopus.com/inward/citedby.url?scp=17644415702&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2005.03.004
DO - 10.1016/j.mcn.2005.03.004
M3 - Article
C2 - 15950153
AN - SCOPUS:17644415702
VL - 29
SP - 372
EP - 380
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
SN - 1044-7431
IS - 3
ER -