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Conditional expression of Hoxa2 gene in CG4 cells favours proliferation over differentiation of a myelinating phenotype
Author(s) -
Wang Monica Juan,
Doucette J. Ronald,
Nazarali Adil J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a879-d
Subject(s) - biology , phenotype , microbiology and biotechnology , cell culture , gene , homeobox , oligodendrocyte , gene expression , cellular differentiation , progenitor cell , cell growth , transfection , genetics , stem cell , myelin , neuroscience , central nervous system
Oligodendrocyte progenitor cells (OPCs) give rise to oligodendrocytes (OLs) to myelinate axons in CNS, both during development as well as after a demyelinating insult (e.g. multiple sclerosis). One transcription factor (TF), homeobox gene Hoxa2 , was shown to be expressed throughout early oligodendrogenesis (A2B5, O4 and Gal‐C +ve OL cells), but decreased significantly in MBP+ve OLs. The purpose of the present study was to determine the effect of over‐expressing Hoxa2 gene on the proliferation and differentiation of the OL‐like CG4 cells. Tetracycline (Tet)‐inducible gene expression system was employed to develop a genetically modified CG4 cell line (CG4‐Hoxa2). Stable cells were obtained after G418 and Hygromycin selection, respectively. Our results show that over‐expression of Hoxa2 increased the proliferation of these cells by 17±1.3% compared with wild‐type CG4 cells and cells transfected with control vector; there were no significant differences between the two control groups. In addition, up‐regulation of Hoxa2 appeared to increase the number of cells with a bipolar phenotype when fed with a differentiation medium. Stable CG4 cell line in which Hoxa2 expression can be down‐regulated is being developed. These cell lines will prove to be very useful in identifying the role of Hoxa2 gene in oligodendrogenesis (supported by CIHR and the MS Society of Canada).