TY - JOUR
T1 - Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells
AU - Namihira, Masakazu
AU - Kohyama, Jun
AU - Semi, Katsunori
AU - Sanosaka, Tsukasa
AU - Deneen, Benjamin
AU - Taga, Tetsuya
AU - Nakashima, Kinichi
N1 - Funding Information:
We thank T. Honjo (Kyoto University) for CSL-deficient ES cells, Y.E. Sun (University of California, Los Angeles) for Dll3 cDNA, T. Kitamura (University of Tokyo) for pMY vector and Plat-E cells, and F.H. Gage (Salk Institute) for the SOX2-EGFP mouse. We appreciate Y. Bessho and T. Matsui for valuable discussions. We wish to thank the members of our laboratories, in particular I. Nobuhisa, for technical suggestions. We also thank I. Smith for helpful comments and critical reading of the manuscript. We are very grateful to M. Ueda for excellent secretarial assistance. Many thanks to N. Namihira for technical help. This work has been supported by a Grant-in-Aid for Young Scientists, a Grant-in-Aid for Scientific Research on priority areas, the NAIST Global COE Program (Frontier Biosciences: Strategies for Survival and Adaptation in a Changing Global Environment), Kumamoto University COE Program (Cell Fate Regulation Research and Education Unit) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, by CREST from Japan Science and Technology Agency, and by the Nakajima Foundation and the Uehara Memorial Foundation.
PY - 2009/2/17
Y1 - 2009/2/17
N2 - During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor I, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes.
AB - During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor I, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes.
UR - http://www.scopus.com/inward/record.url?scp=59649112849&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649112849&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2008.12.014
DO - 10.1016/j.devcel.2008.12.014
M3 - Article
C2 - 19217426
AN - SCOPUS:59649112849
SN - 1534-5807
VL - 16
SP - 245
EP - 255
JO - Developmental Cell
JF - Developmental Cell
IS - 2
ER -