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Identification of Positionally Distinct Astrocyte Subtypes whose Identities Are Specified by a Homeodomain Code

Hochstim, Christian and Deneen, Benjamin and Lukaszewicz, Agnès I. and Zhou, Qiao and Anderson, David J. (2008) Identification of Positionally Distinct Astrocyte Subtypes whose Identities Are Specified by a Homeodomain Code. Cell, 133 (3). pp. 510-522. ISSN 0092-8674. PMCID PMC2394859. doi:10.1016/j.cell.2008.02.046.

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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.

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Anderson, David J.0000-0001-6175-3872
Alternate Title:The spinal cord contains positionally distinct astrocyte subtypes whose identities are specified by a homeodomain transcriptional code
Additional Information:© 2015 Elsevier Inc. Under an Elsevier user license. Received: September 9, 2007; Revised: December 20, 2007; Accepted: February 11, 2008; Published: May 1, 2008. We thank A. Stoykova, P. Gruss, and G. Lanuza for sharing Pax6-lacZ mice and embryos, M. Tessier-Lavigne for the Slit1-GFP mice, and K. McCarthy for pilot experiments with GFAP-CreER mice. We also thank T. Jessell for helpful discussions and antibodies, and E. Laufer and G. D'Arcangelo for in situ probes and antibody reagents. We thank S. Pease, J. Alex, and the staff of the Caltech animal facility for assistance with mouse breeding and timed matings; R. Diamond for assistance with FACS; E. Zuo for Affymetrix microarray hybridization; P. Lwigale for advice and assistance with electroporation and egg husbandry techniques; M. Martinez for genotyping mouse lines; J. Chow, M. Lee, R. Ho, and J. S. Chang for technical assistance; G. Mosconi for laboratory management; and G. Mancuso for administrative assistance. This work was supported in part by NIH grant 1R01-NS23476. D.J.A. is an Investigator of the Howard Hughes Medical Institute.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:MOLNEURO; DEVBIO
Issue or Number:3
PubMed Central ID:PMC2394859
Record Number:CaltechAUTHORS:20150305-115604802
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Official Citation:Hochstim, C., Deneen, B., Lukaszewicz, A., Zhou, Q., & Anderson, D. J. (2008). Identification of Positionally Distinct Astrocyte Subtypes whose Identities Are Specified by a Homeodomain Code. Cell, 133(3), 510-522. doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55545
Deposited On:05 Mar 2015 22:31
Last Modified:10 Nov 2021 20:47

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