Pax6 Controls Astrocyte Positional Identity in the Spinal Cord

Citation

Hochstim, Christian John (2007) Pax6 Controls Astrocyte Positional Identity in the Spinal Cord. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/KSPD-J220. https://resolver.caltech.edu/CaltechETD:etd-07262008-115538

Abstract

Astrocytes constitute the most abundant cell type in the 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 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 re-utilized following the specification of neuronal identity earlier in development.

Thesis Files