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Opposing roles for Hoxa2 and Hoxb2 in hindbrain oligodendrocyte patterning.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Nov 28; Vol. 32 (48), pp. 17172-85. - Publication Year :
- 2012
-
Abstract
- 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 Hox genes, 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.
- Subjects :
- Animals
Body Patterning genetics
Cell Proliferation
Gene Expression Regulation, Developmental
Homeobox Protein Nkx-2.2
Homeodomain Proteins metabolism
Mice
Mice, Knockout
Myelin Sheath genetics
Myelin Sheath metabolism
Rhombencephalon embryology
Transcription Factors metabolism
Cell Differentiation genetics
Homeodomain Proteins genetics
Oligodendroglia metabolism
Rhombencephalon metabolism
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 32
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 23197710
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.0885-12.2012