QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 20 February 2008
doi: 10.1242/dev.015370

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.015370v1 135/7/1271    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sugimori, M. Articles by Nakafuku, M. Search for Related Content PubMed PubMed Citation Articles by Sugimori, M. Articles by Nakafuku, M. Social Bookmarking                         What's this?

Ascl1 is required for oligodendrocyte development in the spinal cord

¹ Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
² Biologie des Interactions Neurones/Glie, Unite Mixte de Recherche INSERM U-711, UPMC Hopital de la Salpetriere, 75651 Paris cedex 13, France.
³ Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
⁴ Departments of Pediatrics and Neurosurgery, University of Cincinnati College of Medicine, 125 Eden Avenue, Cincinnati, OH 45267, USA.
⁵ Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, 3-4-15, Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan.

^* Author for correspondence (e-mail: masato.nakafuku{at}cchmc.org)

Accepted 17 January 2008

Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitors (OLPs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. How these distinct steps are controlled remains unclear. Our previous study demonstrated an important role of the helix-loop-helix (HLH) transcription factor Ascl1 in early generation of OLPs in the developing spinal cord. Here, we show that Ascl1 is also involved in terminal differentiation of oligodendrocytes late in development. Ascl1^-/- mutant mice showed a deficiency in differentiation of myelin-expressing oligodendrocytes at birth. In vitro culture studies demonstrate that the induction and maintenance of co-expression of Olig2 and Nkx2-2 in OLPs, and thyroid hormone-responsive induction of myelin proteins are impaired in Ascl1^-/- mutants. Gain-of-function studies further showed that Ascl1 collaborates with Olig2 and Nkx2-2 in promoting differentiation of OLPs into oligodendrocytes in vitro. Overexpression of Ascl1, Olig2 and Nkx2-2 alone stimulated the specification of OLPs, but the combinatorial action of Ascl1 and Olig2 or Nkx2-2 was required for further promoting their differentiation into oligodendrocytes. Thus, Ascl1 regulates multiple aspects of oligodendrocyte development in the spinal cord.

Key words: Cell fate, Oligodendrocyte, Myelin, Glia, Stem cell, Transcription factor, HLH factor, Spinal cord, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B.-Y. Hu, Z.-W. Du, X.-J. Li, M. Ayala, and S.-C. Zhang Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects Development, May 1, 2009; 136(9): 1443 - 1452. [Abstract] [Full Text] [PDF]

				M. Fahling, R. Mrowka, A. Steege, K. M. Kirschner, E. Benko, B. Forstera, P. B. Persson, B. J. Thiele, J. C. Meier, and H. Scholz Translational Regulation of the Human Achaete-scute Homologue-1 by Fragile X Mental Retardation Protein J. Biol. Chem., February 13, 2009; 284(7): 4255 - 4266. [Abstract] [Full Text] [PDF]

				C. Galichet, F. Guillemot, and C. M. Parras Neurogenin 2 has an essential role in development of the dentate gyrus Development, June 1, 2008; 135(11): 2031 - 2041. [Abstract] [Full Text] [PDF]