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Published February 17, 2009 | Supplemental Material
Journal Article Open

Committed neuronal precursors confer astrocytic potential on residual neural precursor cells

Abstract

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.

Additional Information

© 2008 Elsevier B.V. Received 30 June 2008; revised 1 December 2008; accepted 30 December 2008. Published: February 16, 2009. Available online 17 February 2009. 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.

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