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IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.

Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K, Gage FH - J. Cell Biol. (2004)

Bottom Line: Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling.Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers.These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT
Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

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IGF-I induction of oligodendrocyte differentiation is associated with an up-regulation of BMP antagonists Noggin, Smad6, and Smad7. Q-PCR analysis and quantification of relative fold change (normalized to expression levels under FGF-2 conditions) of Noggin, Smad6, and Smad7. RNA was harvested from 24-h cultures treated with 20 ng/ml FGF-2, 500 ng/ml IGF-I, or both. All error bars represent SDs.
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fig6: IGF-I induction of oligodendrocyte differentiation is associated with an up-regulation of BMP antagonists Noggin, Smad6, and Smad7. Q-PCR analysis and quantification of relative fold change (normalized to expression levels under FGF-2 conditions) of Noggin, Smad6, and Smad7. RNA was harvested from 24-h cultures treated with 20 ng/ml FGF-2, 500 ng/ml IGF-I, or both. All error bars represent SDs.

Mentions: If IGF-I induction of oligodendrocyte differentiation involves the inhibition of BMP signaling, a change in the expression of BMP antagonists upon IGF-I treatment might be observed. In addition to extracellular antagonists of BMP signaling, such as Noggin, intracellular proteins that can interfere with downstream BMP receptor signaling, called inhibitory Smads (Smad6, Smad7), have also been identified (Christian and Nakayama, 1999). Therefore, we performed Q-PCR analysis of cultures treated with 500 ng/ml IGF-I for 24 h and examined the relative fold change of Noggin, Smad6, and Smad7 (Fig. 6; all values were normalized to expression levels under FGF-2 conditions). Expression of Noggin and Smad6 increased by at least four- and sixfold, respectively, after IGF-I treatment. There was only a slight increase in Smad7 levels with IGF-I treatment (∼1.2-fold). In each case, if IGF-I–treated cultures included 20 ng/ml FGF-2, the up-regulation of BMP antagonists was not observed, suggesting that FGF-2 can suppress the IGF-I–mediated up-regulation of Noggin and Smad6. Together, these results suggest that IGF-I–instructive effects on oligodendrocyte differentiation are mediated, at least in part, through an inhibition of BMP signaling.


IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.

Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K, Gage FH - J. Cell Biol. (2004)

IGF-I induction of oligodendrocyte differentiation is associated with an up-regulation of BMP antagonists Noggin, Smad6, and Smad7. Q-PCR analysis and quantification of relative fold change (normalized to expression levels under FGF-2 conditions) of Noggin, Smad6, and Smad7. RNA was harvested from 24-h cultures treated with 20 ng/ml FGF-2, 500 ng/ml IGF-I, or both. All error bars represent SDs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171962&req=5

fig6: IGF-I induction of oligodendrocyte differentiation is associated with an up-regulation of BMP antagonists Noggin, Smad6, and Smad7. Q-PCR analysis and quantification of relative fold change (normalized to expression levels under FGF-2 conditions) of Noggin, Smad6, and Smad7. RNA was harvested from 24-h cultures treated with 20 ng/ml FGF-2, 500 ng/ml IGF-I, or both. All error bars represent SDs.
Mentions: If IGF-I induction of oligodendrocyte differentiation involves the inhibition of BMP signaling, a change in the expression of BMP antagonists upon IGF-I treatment might be observed. In addition to extracellular antagonists of BMP signaling, such as Noggin, intracellular proteins that can interfere with downstream BMP receptor signaling, called inhibitory Smads (Smad6, Smad7), have also been identified (Christian and Nakayama, 1999). Therefore, we performed Q-PCR analysis of cultures treated with 500 ng/ml IGF-I for 24 h and examined the relative fold change of Noggin, Smad6, and Smad7 (Fig. 6; all values were normalized to expression levels under FGF-2 conditions). Expression of Noggin and Smad6 increased by at least four- and sixfold, respectively, after IGF-I treatment. There was only a slight increase in Smad7 levels with IGF-I treatment (∼1.2-fold). In each case, if IGF-I–treated cultures included 20 ng/ml FGF-2, the up-regulation of BMP antagonists was not observed, suggesting that FGF-2 can suppress the IGF-I–mediated up-regulation of Noggin and Smad6. Together, these results suggest that IGF-I–instructive effects on oligodendrocyte differentiation are mediated, at least in part, through an inhibition of BMP signaling.

Bottom Line: Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling.Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers.These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT
Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

Show MeSH