Conditional Tet-regulated over-expression of Hoxa2 in CG4 cells increases their proliferation and delays their differentiation into oligodendrocyte-like cells expressing myelin basic protein

Cell Mol Neurobiol. 2011 Aug;31(6):875-86. doi: 10.1007/s10571-011-9685-2. Epub 2011 Apr 9.

Abstract

Hoxa2 gene was reported to be expressed by oligodendrocytes (OLs) and down-regulated at the terminal differentiation stage during oligodendrogenesis in mice (Nicolay et al. 2004b). To further investigate the role of Hoxa2 in oligodendroglial development, a tetracycline regulated controllable expression system was utilized to establish a stable cell line (CG4-SHoxa2 [sense Hoxa2]), where the expression level of Hoxa2 gene could be up-regulated. The impact of Hoxa2 over-expression on the proliferation and differentiation of CG4-SHoxa2 cells was investigated. Up-regulation of Hoxa2 increased the proliferation of CG4-SHoxa2 cells. The mRNA levels of PDGFαR (platelet-derived growth factor [PDGF] alpha receptor), which is expressed by OL progenitor cells, were not different in CG4-SHoxa2 cells compared to wild-type CG4 cells. Semi-quantitative RT-PCR revealed that the mRNA levels of myelin basic protein (MBP) was lower in CG4-SHoxa2 cells than in wild-type CG4 cells indicating the differentiation of CG4-SHoxa2 cells was delayed when the Hoxa2 gene was up-regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Gangliosides / metabolism
  • Gene Expression Regulation / drug effects
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism*
  • Oligodendroglia / cytology*
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tetracycline / pharmacology*

Substances

  • Gangliosides
  • Homeodomain Proteins
  • Hoxa11 protein, rat
  • Myelin Basic Protein
  • RNA, Messenger
  • ganglioside A2B5
  • Receptor, Platelet-Derived Growth Factor alpha
  • Tetracycline
  • Bromodeoxyuridine