Calcium receptor expression and function in oligodendrocyte commitment and lineage progression: potential impact on reduced myelin basic protein in CaR-null mice.
Oligodendrocytes develop from oligodendrocyte progenitor cells (OPCs), which in turn arise from a subset of neuroepithelial precursor cells during midneurogenesis. Development of the oligodendrocyte lineage involves a plethora of cell-intrinsic and -extrinsic signals. A cell surface calcium-sensing receptor (CaR) has been shown to be functionally expressed in immature oligodendrocytes. Here, we investigated the expression and function of the CaR during oligodendrocyte development. We show that the order of CaR mRNA expression as assessed by quantitative polymerase chain reaction is mature oligodendrocyte > neuron > astrocyte. We next determined the rank order of CaR expression on inducing specification of neural stem cells to the neuronal, oligodendroglial, or astrocytic lineages and found that the relative levels of CaR mRNA expression are OPC > neuron > astrocytes. CaR mRNA expression in cells at various stages of development along the oligodendrocyte lineage revealed that its expression is robustly up-regulated during the OPC stage and remains high until the premyelinating stage, decreasing thereafter by severalfold in the mature oligodendrocyte. In OPCs, high Ca(2+) acting via the CaR promotes cellular proliferation. We further observed that high Ca(2+) stimulates the mRNA levels of myelin basic protein in preoligodendrocytes, which is also CaR mediated. Finally, myelin basic protein levels were significantly reduced in the cerebellum of CaR-null mice during development. Our results show that CaR expression is up-regulated when neural stem cells are specified to the oligodendrocyte lineage and that activation of the receptor results in OPC expansion and differentiation. We conclude that the CaR may be a novel regulator of oligodendroglial development and function.
Chattopadhyay
Naibedya
N
Department of Medicine and Membrane Biology Program, Division of Endocrinology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Espinosa-Jeffrey
Araceli
A
Tfelt-Hansen
Jacob
J
Yano
Shozo
S
Bandyopadhyay
Sanghamitra
S
Brown
Edward M
EM
de Vellis
Jean
J
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing