Abstract
In the developing mouse brain, the highest Bcl-XL expression is seen at the peak of neurogenesis, whereas the peak of Bax expression coincides with the astrogenic period. While such observations suggest an active role of the Bcl-2 family proteins in the generation of neurons and astrocytes, no definitive demonstration has been provided to date. Using combinations of gain- and loss-of-function assays in vivo and in vitro, we provide evidence for instructive roles of these proteins in neuronal and astrocytic fate specification. Specifically, in Bax knockout mice, astrocyte formation was decreased in the developing cortices. Overexpression of Bcl-XL and Bax in embryonic cortical precursors induced neural and astrocytic differentiation, respectively, while inhibitory RNAs led to the opposite results. Importantly, inhibition of caspase activity, dimerization, or mitochondrial localization of Bcl-XL/Bax proteins indicated that the differentiation effects of Bcl-XL/Bax are separable from their roles in cell survival and apoptosis. Lastly, we describe activation of intracellular signaling pathways and expression of basic helix-loop-helix transcriptional factors specific for the Bcl-2 protein-mediated differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 4293-4305 |
| Number of pages | 13 |
| Journal | Molecular and cellular biology |
| Volume | 27 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jun 1 2007 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Cite this
Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells. / Chang, Mi Yoon; Sun, Woong; Ochiai, Wataru; Nakashima, Kinichi; Kim, Soo Young; Park, Chang Hwan; Kang, Jin Sun; Shim, Jae Won; Jo, A. Young; Kang, Chun Sik; Lee, Yong Sung; Kim, Jae Sang; Lee, Sang Hun.
In: Molecular and cellular biology, Vol. 27, No. 12, 01.06.2007, p. 4293-4305.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells
AU - Chang, Mi Yoon
AU - Sun, Woong
AU - Ochiai, Wataru
AU - Nakashima, Kinichi
AU - Kim, Soo Young
AU - Park, Chang Hwan
AU - Kang, Jin Sun
AU - Shim, Jae Won
AU - Jo, A. Young
AU - Kang, Chun Sik
AU - Lee, Yong Sung
AU - Kim, Jae Sang
AU - Lee, Sang Hun
PY - 2007/6/1
Y1 - 2007/6/1
N2 - In the developing mouse brain, the highest Bcl-XL expression is seen at the peak of neurogenesis, whereas the peak of Bax expression coincides with the astrogenic period. While such observations suggest an active role of the Bcl-2 family proteins in the generation of neurons and astrocytes, no definitive demonstration has been provided to date. Using combinations of gain- and loss-of-function assays in vivo and in vitro, we provide evidence for instructive roles of these proteins in neuronal and astrocytic fate specification. Specifically, in Bax knockout mice, astrocyte formation was decreased in the developing cortices. Overexpression of Bcl-XL and Bax in embryonic cortical precursors induced neural and astrocytic differentiation, respectively, while inhibitory RNAs led to the opposite results. Importantly, inhibition of caspase activity, dimerization, or mitochondrial localization of Bcl-XL/Bax proteins indicated that the differentiation effects of Bcl-XL/Bax are separable from their roles in cell survival and apoptosis. Lastly, we describe activation of intracellular signaling pathways and expression of basic helix-loop-helix transcriptional factors specific for the Bcl-2 protein-mediated differentiation.
AB - In the developing mouse brain, the highest Bcl-XL expression is seen at the peak of neurogenesis, whereas the peak of Bax expression coincides with the astrogenic period. While such observations suggest an active role of the Bcl-2 family proteins in the generation of neurons and astrocytes, no definitive demonstration has been provided to date. Using combinations of gain- and loss-of-function assays in vivo and in vitro, we provide evidence for instructive roles of these proteins in neuronal and astrocytic fate specification. Specifically, in Bax knockout mice, astrocyte formation was decreased in the developing cortices. Overexpression of Bcl-XL and Bax in embryonic cortical precursors induced neural and astrocytic differentiation, respectively, while inhibitory RNAs led to the opposite results. Importantly, inhibition of caspase activity, dimerization, or mitochondrial localization of Bcl-XL/Bax proteins indicated that the differentiation effects of Bcl-XL/Bax are separable from their roles in cell survival and apoptosis. Lastly, we describe activation of intracellular signaling pathways and expression of basic helix-loop-helix transcriptional factors specific for the Bcl-2 protein-mediated differentiation.
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UR - http://www.scopus.com/inward/citedby.url?scp=34250155977&partnerID=8YFLogxK
U2 - 10.1128/MCB.00031-07
DO - 10.1128/MCB.00031-07
M3 - Article
C2 - 17438128
AN - SCOPUS:34250155977
VL - 27
SP - 4293
EP - 4305
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 12
ER -