Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code.
Astrocytes constitute the most abundant cell type in the central nervous system (CNS) and play diverse functional roles, but the ontogenetic origins of this phenotypic diversity are poorly understood. We have investigated whether positional identity, a fundamental organizing principle governing the generation of neuronal subtype diversity, is also relevant to astrocyte diversification. We identified three positionally distinct subtypes of white-matter astrocytes (WMA) in the spinal cord, which can be distinguished by the combinatorial expression of Reelin and Slit1. These astrocyte subtypes derive from progenitor domains expressing the homeodomain transcription factors Pax6 and Nkx6.1, respectively. Loss- and gain-of-function experiments indicate that the positional identity of these astrocyte subtypes is controlled by Pax6 and Nkx6.1 in a combinatorial manner. Thus, positional identity is an organizing principle underlying astrocyte, as well as neuronal, subtype diversification and is controlled by a homeodomain transcriptional code whose elements are reutilized following the specification of neuronal identity earlier in development.
Hochstim
Christian
C
Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Deneen
Benjamin
B
Lukaszewicz
Agnès
A
Zhou
Qiao
Q
Anderson
David J
DJ
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D000091042:Reelin Protein; D012097:Repressor Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D014158:Transcription, Genetic
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C491328:Nkx6-1 protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D000091042:Reelin Protein; D012097:Repressor Proteins; C120010:Slit1 protein, mouse; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases