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Identification of the Tctex‐1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain
Author(s) -
Tseng YunYu,
Gruzdeva Natalia,
Li Aiqun,
Chuang JenZen,
Sung ChingHwa
Publication year - 2010
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22402
Subject(s) - biology , neurogenesis , subgranular zone , dentate gyrus , neural stem cell , microbiology and biotechnology , nestin , progenitor cell , green fluorescent protein , reporter gene , subventricular zone , stem cell , neuroscience , gene expression , hippocampus , genetics , gene
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. J. Comp. Neurol. 518:3327–3342, 2010. © 2010 Wiley‐Liss, Inc.