Discoidin domain receptor 1, a tyrosine kinase receptor, is upregulated in an experimental model of remyelination and during oligodendrocyte differentiation in vitro.
The discoidin domain receptor (DDR1) is highly expressed in oligodendrocytes during the neurodevelopmental myelination process and is genetically associated to schizophrenia. In this study, we aimed to further assess the involvement of DDR1 in both remyelination and oligodendrocyte differentiation. In the mouse model of demyelination-remyelination induced by oral administration of cuprizone, in situ hybridization showed an upregulation of the DDR1 gene in three different white matter areas (corpus callosum, dorsal fornix, and external capsule) during the remyelination period. Moreover, real time reverse transcriptase polymerase chain reaction showed that the increase in DDR1 messenger RNA (mRNA) was strongly correlated with the number of DDR1-positive cells in the corpus callosum (Spearman coefficient = 0.987, P = 0.013). Cells positive for DDR1 mRNA were also positive for oligodendrocyte markers (OLIG2, carnosine, and APC) but not for markers of oligodendrocyte precursors (NG2), myelin markers (CNPase), microglia (CD11b), or reactive glia (GFAP). Differentiation of a human oligodendroglial cell line, HOG16, was associated with an increase in mRNA expression of DDR1 and several myelin proteins (MBP and MOBP) but not other proteins (APC and CNPase). Here, we demonstrate that DDR1 is upregulated in vitro and in vivo when oligodendrocyte myelinating machinery is activated. Further studies are needed to identify the specific molecular pathway.
Unitat de Psiquiatria i Psicologia Mèdica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C/Sant Llorenç 21, 43201, Reus, Spain.
Neus
N
Franco-Pons
Jordi
J
Tomàs
Bárbara
B
Roig
Carme
C
Auladell
Lourdes
L
Martorell
Elisabet
E
Vilella
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003337:Corpus Callosum / Q000166:cytology / Q000378:metabolism; D003471:Cuprizone / Q000008:administration & dosage; D000070818:Discoidin Domain Receptors; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011975:Receptors, Mitogen / Q000096:biosynthesis* / Q000235:genetics; D012559:Schizophrenia / Q000378:metabolism*; D015854:Up-Regulation
D008996:Monoamine Oxidase Inhibitors; D009185:Myelin Proteins; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D003471:Cuprizone; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases