Identification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain.

TitleIdentification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain.
Publication TypeJournal Article
Year of Publication2010
AuthorsTseng Y-Y, Gruzdeva N, Li A, Chuang J-Z, Sung C-H
JournalJ Comp Neurol
Volume518
Issue16
Pagination3327-42
Date Published2010 Aug 15
ISSN1096-9861
KeywordsAnimals, Brain, Cell Line, Dyneins, Gene Expression Regulation, Humans, Intermediate Filament Proteins, Mice, Mice, Transgenic, Nerve Tissue Proteins, Nestin, Neurons, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Stem Cells
Abstract

Previous studies showed that Tctex-1 immunoreactivity is selectively enriched in the germinal zones of adult brain. In this report we identify a regulatory region of the Tctex-1 gene that is capable of directing transgenic expression of green fluorescent protein (GFP) reporter that recapitulates the spatial and temporal expression pattern of endogenous Tctex-1. This construct specifically targeted expression to the nestin(+)/Pax6(+)/GLAST(+) radial glial cells and Tbr2(+) intermediate progenitors when the reporter construct was delivered to developing mouse neocortex via in utero electroporation. Characterization of mice transgenically expressing GFP under the same regulatory element showed that the GFP expression is faithful to endogenous Tctex-1 at the subgranular zone (SGZ) of dentate gyrus, ventricular/subventricular zone of lateral ventricles, and ependymal layer of 3rd ventricle of adult brains. Immunolocalization and bromodeoxyuridine incorporation studies of adult SGZ in four independent mouse lines showed that Tctex-1:GFP reporter selectively marks nestin(+)/GFAP(+)/Sox2(+) neural stem-like cells in two mouse lines (4 and 13). In two other mouse lines (17 and 18), Tctex-1:GFP is selectively expressed in Type-2 and Type-3 transient amplifying progenitors and a small subset of young neuronal progeny. The P/E-Tctex-1 reporter mouse studies independently confirmed the specific enrichment of Tctex-1 at adult SGZ stem/progenitor cells. Furthermore, these studies supported the notion that an analogous transcriptional program may be used to regulate neurogenesis in embryonic cerebral cortex and adult hippocampus. Finally, the genomic sequences and the reporter mouse lines described here provide useful experimental tools to advance adult neural stem cell research.

DOI10.1002/cne.22402
Alternate JournalJ. Comp. Neurol.
PubMed ID20575070
PubMed Central IDPMC2899893
Grant ListEY11307 / EY / NEI NIH HHS / United States
R01 EY011307-12 / EY / NEI NIH HHS / United States
R01 EY011307-14 / EY / NEI NIH HHS / United States
R01 EY011307-15 / EY / NEI NIH HHS / United States
R01 EY011307 / EY / NEI NIH HHS / United States
R01 EY011307-13 / EY / NEI NIH HHS / United States