Abstract
Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Magnetic resonance imaging (MRI) of BFPP brains reveals myelination defects in addition to brain malformation. However, the cellular role of GPR56 in oligodendrocyte development remains unknown. Here, we demonstrate that loss of Gpr56 leads to hypomyelination of the central nervous system in mice. GPR56 levels are abundant throughout early stages of oligodendrocyte development, but are downregulated in myelinating oligodendrocytes. Gpr56-knockout mice manifest with decreased oligodendrocyte precursor cell (OPC) proliferation and diminished levels of active RhoA, leading to fewer mature oligodendrocytes and a reduced number of myelinated axons in the corpus callosum and optic nerves. Conditional ablation of Gpr56 in OPCs leads to a reduced number of mature oligodendrocytes as seen in constitutive knockout of Gpr56. Together, our data define GPR56 as a cell-autonomous regulator of oligodendrocyte development.
| Original language | English (US) |
|---|---|
| Article number | 7121 |
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| State | Published - Jan 21 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. / Giera, Stefanie; Deng, Yiyu; Luo, Rong; Ackerman, Sarah D.; Mogha, Amit; Monk, Kelly; Ying, Yanqin; Jeong, Sung Jin; Makinodan, Manabu; Bialas, Allison R.; Chang, Bernard S.; Stevens, Beth; Corfas, Gabriel; Piao, Xianhua.
In: Nature Communications, Vol. 6, 7121, 21.01.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development
AU - Giera, Stefanie
AU - Deng, Yiyu
AU - Luo, Rong
AU - Ackerman, Sarah D.
AU - Mogha, Amit
AU - Monk, Kelly
AU - Ying, Yanqin
AU - Jeong, Sung Jin
AU - Makinodan, Manabu
AU - Bialas, Allison R.
AU - Chang, Bernard S.
AU - Stevens, Beth
AU - Corfas, Gabriel
AU - Piao, Xianhua
PY - 2015/1/21
Y1 - 2015/1/21
N2 - Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Magnetic resonance imaging (MRI) of BFPP brains reveals myelination defects in addition to brain malformation. However, the cellular role of GPR56 in oligodendrocyte development remains unknown. Here, we demonstrate that loss of Gpr56 leads to hypomyelination of the central nervous system in mice. GPR56 levels are abundant throughout early stages of oligodendrocyte development, but are downregulated in myelinating oligodendrocytes. Gpr56-knockout mice manifest with decreased oligodendrocyte precursor cell (OPC) proliferation and diminished levels of active RhoA, leading to fewer mature oligodendrocytes and a reduced number of myelinated axons in the corpus callosum and optic nerves. Conditional ablation of Gpr56 in OPCs leads to a reduced number of mature oligodendrocytes as seen in constitutive knockout of Gpr56. Together, our data define GPR56 as a cell-autonomous regulator of oligodendrocyte development.
AB - Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Magnetic resonance imaging (MRI) of BFPP brains reveals myelination defects in addition to brain malformation. However, the cellular role of GPR56 in oligodendrocyte development remains unknown. Here, we demonstrate that loss of Gpr56 leads to hypomyelination of the central nervous system in mice. GPR56 levels are abundant throughout early stages of oligodendrocyte development, but are downregulated in myelinating oligodendrocytes. Gpr56-knockout mice manifest with decreased oligodendrocyte precursor cell (OPC) proliferation and diminished levels of active RhoA, leading to fewer mature oligodendrocytes and a reduced number of myelinated axons in the corpus callosum and optic nerves. Conditional ablation of Gpr56 in OPCs leads to a reduced number of mature oligodendrocytes as seen in constitutive knockout of Gpr56. Together, our data define GPR56 as a cell-autonomous regulator of oligodendrocyte development.
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U2 - 10.1038/ncomms7121
DO - 10.1038/ncomms7121
M3 - Article
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7121
ER -