Ascl1 is required for oligodendrocyte development in the spinal cord
| Autor: | François Guillemot, Hiroko Nakatani, Carlos Parras, Michiya Sugimori, Motoshi Nagao, Mélanie Lebel, Masato Nakafuku |
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| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Oligodendrocyte Transcription Factor 2 Central nervous system Nerve Tissue Proteins Biology Models Biological Rats Sprague-Dawley OLIG2 Mice Myelin stomatognathic system Basic Helix-Loop-Helix Transcription Factors medicine Animals Molecular Biology Cells Cultured Homeodomain Proteins Stem Cells Cell Differentiation Zebrafish Proteins Embryonic stem cell Mice Mutant Strains Oligodendrocyte Rats Cell biology Oligodendroglia ASCL1 Homeobox Protein Nkx-2.2 medicine.anatomical_structure Spinal Cord Immunology Transcription Factors Developmental Biology |
| Zdroj: | Development. 135:1271-1281 |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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