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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

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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.

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Abbreviations

ANOVA:

Analysis of variance

A–P:

Anterior–posterior

BrdU:

Bromodeoxyuridine

CDK:

Cyclin-dependent protein kinase

CNS:

Central nervous system

DM:

Differentiation medium

DMEM:

Dulbecco’s modified eagle medium

Dox:

Doxycycline

EDTA:

Ethylenediaminetetraacetic acid

ES:

Embryonic stem cells

FITC:

Fluorescein isothiocyanate

GalC:

Galactocerebroside C

GM:

Growth medium

Hyg:

Hygromycin

MBP:

Myelin basic protein

mRNA:

Messenger ribonucleic acid

Myc:

c-myc gene/protein

Nkx2.2:

NK2 transcription factor related, locus 2

Nkx6.1:

NK6 transcription factor related, locus 1

O-2A:

Oligodendrocyte-type 2 astrocyte

OL(s):

Oligodendrocyte(s)

Olig1/2:

Oligodendrocyte lineage gene 1/2

OPC(s):

Oligodendrocyte precursor cell(s)

p27/Kip1:

Kinase inhibitory protein 1

PBS:

Phosphate buffered saline

PDGF:

Platelet-derived growth factor

PDGFαR:

Platelet-derived growth factor receptor α

RIPA:

Radioimmunoprecipitation assay

RT:

Room temperature

RT-PCR:

Reverse transcription polymerase chain reaction

SHoxa2:

Sense Hoxa2

Sox:

SRY-box containing gene

Taq :

Thermus aquaticus

Tet:

Tetracycline

tTA:

Tetracycline transcriptional activator

TF(s):

Transcription factor(s)

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Acknowledgments

We dedicate this manuscript to Marshall Nirenberg, who is remembered for his pioneering work in deciphering the genetic code and in whose lab AJN first cloned the Hoxa2 (Hox1.11) gene. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) to AJN and JRD.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, College of Pharmacy and Nutrition, University of Saskatchewan, 116 Thorvaldson Building, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada

    Monica Wang & Adil J. Nazarali

  2. Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada

    J. Ronald Doucette

  3. Cameco Multiple Sclerosis Neuroscience Research Center, City Hospital, Saskatoon, SK, Canada

    J. Ronald Doucette & Adil J. Nazarali

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  1. Monica Wang
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Correspondence to Adil J. Nazarali.

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Wang, M., Doucette, J.R. & Nazarali, A.J. 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 31, 875–886 (2011). https://doi.org/10.1007/s10571-011-9685-2

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