Abstract
How a pool of undifferentiated neural progenitor cells is maintained in the developing nervous system is an issue that remains unresolved. One of the key transcription factors for self-renewal of these cells is Sox2, the forced expression of which has been shown to inhibit neuronal differentiation in vivo. To dissect the molecular mechanisms of Sox2 activity, a ChIP-on-chip assay has been carried out for Sox2, and multiple candidate direct target genes have been isolated. In this report, we provide evidence indicating that Sox6, which like Sox2 belongs to the SRY-related HMG box transcription factor family, is a bona-fide direct regulatory target of Sox2. In vivo, Sox6 expression is seen with a temporal lag in Sox2-positive neural precursor cells in the ventricular zone, and Sox2 promotes expression of Sox6 as a transcriptional activator. Interestingly, gain- and loss-of-function assays indicate that Sox6 in turn is required for the maintenance of Sox2 expression, suggesting that a positive feedback loop, which functions to inhibit premature neuronal differentiation, exists between the two transcription factors.
| Original language | English |
|---|---|
| Pages (from-to) | 2794-2799 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 111 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2014 Feb 18 |
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Keywords
- CNS
- Neural development
- Neural stem cell
- SoxB1
- SoxD
ASJC Scopus subject areas
- General
Cite this
Positive feedback loop between Sox2 and Sox6 inhibits neuronal differentiation in the developing central nervous system. / Lee, Kyung Eun; Seo, Jihae; Shin, Jiheon; Ji, Eun Hye; Roh, Jiwon; Kim, Joo Yeon; Sun, Woong; Muhr, Jonas; Lee, Sanghyuk; Kim, Jaesang.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 7, 18.02.2014, p. 2794-2799.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Positive feedback loop between Sox2 and Sox6 inhibits neuronal differentiation in the developing central nervous system
AU - Lee, Kyung Eun
AU - Seo, Jihae
AU - Shin, Jiheon
AU - Ji, Eun Hye
AU - Roh, Jiwon
AU - Kim, Joo Yeon
AU - Sun, Woong
AU - Muhr, Jonas
AU - Lee, Sanghyuk
AU - Kim, Jaesang
PY - 2014/2/18
Y1 - 2014/2/18
N2 - How a pool of undifferentiated neural progenitor cells is maintained in the developing nervous system is an issue that remains unresolved. One of the key transcription factors for self-renewal of these cells is Sox2, the forced expression of which has been shown to inhibit neuronal differentiation in vivo. To dissect the molecular mechanisms of Sox2 activity, a ChIP-on-chip assay has been carried out for Sox2, and multiple candidate direct target genes have been isolated. In this report, we provide evidence indicating that Sox6, which like Sox2 belongs to the SRY-related HMG box transcription factor family, is a bona-fide direct regulatory target of Sox2. In vivo, Sox6 expression is seen with a temporal lag in Sox2-positive neural precursor cells in the ventricular zone, and Sox2 promotes expression of Sox6 as a transcriptional activator. Interestingly, gain- and loss-of-function assays indicate that Sox6 in turn is required for the maintenance of Sox2 expression, suggesting that a positive feedback loop, which functions to inhibit premature neuronal differentiation, exists between the two transcription factors.
AB - How a pool of undifferentiated neural progenitor cells is maintained in the developing nervous system is an issue that remains unresolved. One of the key transcription factors for self-renewal of these cells is Sox2, the forced expression of which has been shown to inhibit neuronal differentiation in vivo. To dissect the molecular mechanisms of Sox2 activity, a ChIP-on-chip assay has been carried out for Sox2, and multiple candidate direct target genes have been isolated. In this report, we provide evidence indicating that Sox6, which like Sox2 belongs to the SRY-related HMG box transcription factor family, is a bona-fide direct regulatory target of Sox2. In vivo, Sox6 expression is seen with a temporal lag in Sox2-positive neural precursor cells in the ventricular zone, and Sox2 promotes expression of Sox6 as a transcriptional activator. Interestingly, gain- and loss-of-function assays indicate that Sox6 in turn is required for the maintenance of Sox2 expression, suggesting that a positive feedback loop, which functions to inhibit premature neuronal differentiation, exists between the two transcription factors.
KW - CNS
KW - Neural development
KW - Neural stem cell
KW - SoxB1
KW - SoxD
UR - http://www.scopus.com/inward/record.url?scp=84894345544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894345544&partnerID=8YFLogxK
U2 - 10.1073/pnas.1308758111
DO - 10.1073/pnas.1308758111
M3 - Article
VL - 111
SP - 2794
EP - 2799
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -