title: Opposing roles for Hoxa2 and Hoxb2 in hindbrain oligodendrocyte patterning.
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.
authors.affiliation: Université Pierre and Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, 75013 Paris, France.
authors.forename: Andrés
authors.initials: A
authors.lastname: Miguez
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ducret
authors.forename: Thomas
authors.initials: T
authors.lastname: Di Meglio
authors.forename: Carlos
authors.initials: C
authors.lastname: Parras
authors.forename: Hatem
authors.initials: H
authors.lastname: Hmidan
authors.forename: Céline
authors.initials: C
authors.lastname: Haton
authors.forename: Sowmya
authors.initials: S
authors.lastname: Sekizar
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Mannioui
authors.forename: Marie
authors.initials: M
authors.lastname: Vidal
authors.forename: Aurélien
authors.initials: A
authors.lastname: Kerever
authors.forename: Omar
authors.initials: O
authors.lastname: Nyabi
authors.forename: Jody
authors.initials: J
authors.lastname: Haigh
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; C490111:Hoxb2 protein, mouse; C000715627:Nkx2-2 protein, mouse; D014157:Transcription Factors