期刊
JOURNAL OF NEUROSCIENCE
卷 32, 期 48, 页码 17172-U603出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0885-12.2012
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资金
- Institut National de la Santeet de la Recherche Medicale
- Novartis Research Foundation
- Federation pour la Recherche sur le Cerveau
- Fondation pour L'Aide a la Recherche sur la Sclerose En Plaques
- Agence Nationale Recherche [08-BLAN-0162-01]
- Swiss National Science Foundation [Sinergia CRSI33_127440]
- Boehringer Ingelheim Fonds
- Neuroscience pole of research in Ile de France
- European Molecular Biology Organization
- European Cooperation in Science and Technology network
- National Institute of Child Health and Human Development
Oligodendrocytes are the myelin-forming cells of the vertebrate CNS. Little is known about the molecular control of region-specific oligodendrocyte development. Here, we show that oligodendrogenesis in the mouse rostral hindbrain, which is organized in a metameric series of rhombomere-derived (rd) territories, follows a rhombomere-specific pattern, with extensive production of oligodendrocytes in the pontine territory (r4d) and delayed and reduced oligodendrocyte production in the prepontine region (r2d, r3d). We demonstrate that segmental organization of oligodendrocytes is controlled by Hoxgenes, namely Hoxa2 and Hoxb2. Specifically, Hoxa2 loss of function induced a dorsoventral enlargement of the Olig2/Nkx2.2-expressing oligodendrocyte progenitor domain, whereas conditional Hoxa2 overexpression in the Olig2(+) domain inhibited oligodendrogenesis throughout the brain. In contrast, Hoxb2 deletion resulted in a reduction of the pontine oligodendrogenic domain. Compound Hoxa2(-/-)/Hoxb2(-/-) mutant mice displayed the phenotype of Hoxb2(-/-) mutants in territories coexpressing Hoxa2 and Hoxb2 (rd3, rd4), indicating that Hoxb2 antagonizes Hoxa2 during rostral hindbrain oligodendrogenesis. This study provides the first in vivo evidence that Hox genes determine oligodendrocyte regional identity in the mammalian brain.
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