Expression of the tyrosine kinase discoidin domain receptor 1 (DDR1) in human central nervous system myelin.
During development of the mouse brain, the protein kinase discoidin domain receptor 1 (DDR1) is present prenatally in neurons of the proliferative areas, and postnatally, DDR1 expression is no longer detected in neurons, but a spatial-temporal expression pattern in oligodendrocytes that overlaps with the dynamics of the myelination process is detected. Notably, oligodendrocytic DDR1 expression is upregulated in mice during experimentally induced remyelination. Recently, we demonstrated that DDR1 expression is high in human brain and that there is an association between the gene and schizophrenia in a case-control study. However, data regarding expression of DDR1 in the human brain are scarce. Here, we describe the expression pattern of DDR1 in the human adult cerebral cortex. Using several immunohistological techniques and in situ hybridization, we identified DDR1 in the following: a) myelin, b) capillary endothelial cells in the gray as well as white matter, and c) in the soma of some oligodendrocytes and astrocytes in the white matter. The most important overall finding in this study was that DDR1 is present in myelin and is expressed by oligodendrocyte cells. We detected the presence of DDR1 mRNA and protein in myelin and observed that DDR1 co-localized with the classical myelin basic protein (MBP). Moreover, we found a strong positive correlation between expression levels of DDR1 and two myelin-associated genes, myelin-associated glycoprotein (MAG) and oligodendrocyte transcription factor 2 (OLIG2). These observations suggest that DDR1 could be an important constituent of myelin. Because defects in myelination are linked to several mental disorders such as schizophrenia, the function of DDR1 in the process of myelination warrants further investigation.
Roig
Bàrbara
B
Hospital Psiquiàtric Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus, Spain.
Franco-Pons
Neus
N
Martorell
Lourdes
L
Tomàs
Jordi
J
Vogel
Wolfgang F
WF
Vilella
Elisabet
E
D001253:Astrocytes / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism*; D000070819:Discoidin Domain Receptor 1; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D009186:Myelin Sheath / Q000737:chemistry* / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; D000070819:Discoidin Domain Receptor 1; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; C405708:OLIG2 protein, human; C092030:DDR1 protein, human