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Giera, Stefanie

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Giera

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Stefanie

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Giera, Stefanie

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2013 - 20183

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Author's Publications: search.filters.isAuthorOfPublication.95e6b919-da06-4d09-81b7-65c456cb6570

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    The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development
    (Nature Pub. Group, 2015) Giera, Stefanie; Deng, Yiyu; Luo, Rong; Ackerman, Sarah D.; Mogha, Amit; Monk, Kelly R.; Ying, Yanqin; Jeong, Sung-Jin; Makinodan, Manabu; Rosen, Allison; Chang, Bernard; Stevens, Beth; Corfas, Gabriel; Piao, Xianhua
    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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    Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells
    (eLife Sciences Publications, Ltd, 2018) Giera, Stefanie; Luo, Rong; Ying, Yanqin; Ackerman, Sarah D; Jeong, Sung-Jin; Stoveken, Hannah M; Folts, Christopher; Welsh, Christina; Tall, Gregory G; Stevens, Beth; Monk, Kelly R; Piao, Xianhua
    In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination.
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    GPR56 Functions Together with α3β1 Integrin in Regulating Cerebral Cortical Development
    (Public Library of Science, 2013) Jeong, Sung-Jin; Luo, Rong; Singer, Kathleen; Giera, Stefanie; Kreidberg, Jordan; Kiyozumi, Daiji; Shimono, Chisei; Sekiguchi, Kiyotoshi; Piao, Xianhua
    Loss of function mutations in GPR56, which encodes a G protein-coupled receptor, cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Studies from BFPP postmortem brain tissue and Gpr56 knockout mice have previously showed that GPR56 deletion leads to breaches in the pial basement membrane (BM) and neuronal ectopias during cerebral cortical development. Since α3β1 integrin also plays a role in pial BM assembly and maintenance, we evaluated whether it functions together with GPR56 in regulating the same developmental process. We reveal that loss of α3 integrin enhances the cortical phenotype associated with Gpr56 deletion, and that neuronal overmigration through a breached pial BM occurs earlier in double knockout than in Gpr56 single knockout mice. These observations provide compelling evidence of the synergism of GPR56 and α3β1 integrin in regulating the development of cerebral cortex.