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Swap70 promotes neural precursor cell cycle exit and oligodendrocyte formation.

ABSTRACT: Multipotent neural precursors produce oligodendrocyte lineage cells, which then migrate throughout the central nervous system and extend multiple, long membrane processes to wrap and myelinate axons. These dynamic cellular behaviors imply dynamic regulation of the cytoskeleton. In a previous microarray screen for new oligodendrocyte genes we identified swap70, which encodes a protein with domains that predict numerous signaling activities. Because mouse Swap70 can promote cell motility by functioning as a guanine nucleotide exchange factor for Rac1, we hypothesized that zebrafish Swap70 promotes oligodendrocyte progenitor cell (OPC) motility and axon wrapping. To test this we investigated Swap70 localization in OPCs and differentiating oligodendrocytes and we performed a series of gain and loss of function experiments. Our tests of gene function did not provide evidence that Swap70 regulates oligodendrocyte lineage cell behavior. Instead, we found that swap70 deficient larvae had excess neural precursors and a deficit of OPCs. Cells associated with neural proliferative zones express swap70. Therefore, our data reveal a potential new role for Swap70 in regulating transition of dividing neural precursors to specified OPCs.

SUBMITTER: Takada N

PROVIDER: S-EPMC3538131 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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swap70 promotes neural precursor cell cycle exit and oligodendrocyte formation.

Takada Norio N Appel Bruce B

Molecular and cellular neurosciences 20110812 3

Multipotent neural precursors produce oligodendrocyte lineage cells, which then migrate throughout the central nervous system and extend multiple, long membrane processes to wrap and myelinate axons. These dynamic cellular behaviors imply dynamic regulation of the cytoskeleton. In a previous microarray screen for new oligodendrocyte genes we identified swap70, which encodes a protein with domains that predict numerous signaling activities. Because mouse Swap70 can promote cell motility by functi ...[more]

PMID: 21875669

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Project description:Experimental autoimmune encephalomyelitis (EAE) is a basic and reliable model used to study clinical and pathological hallmarks of multiple sclerosis (MS) in rodents. Several studies suggest neural precursor cells (NPCs) as a significant research tool while reporting that transplanted NPCs are a promising therapeutic approach to treating neurological disorders, such as MS. The main objective was to approach a preclinical, in vivo scenario of oligodendrogenesis with NPCs, targeting the main chronic demyelinated lumbosacral milieu of EAE, via the least invasive delivery method which is lumbar puncture. We utilized MOG35-55 peptide to induce EAE in C57BL/6 mice and prior to the acute relapse, we intervened with either the traceable GFP+ cellular therapy or saline solution in the intrathecal space of their lumbar spine. A BrdU injection, which enabled us to monitor endogenous proliferation, marked the endpoint 50 days post-induction (50 dpi). Neuropathology with high-throughput, triple immunofluorescent, and transmission electron microscopy (TEM) data were extracted and analyzed. The experimental treatment attenuated the chronic phase of EAE (50 dpi; score <1) following an acute, clinical relapse. Myelination and axonal integrity were rescued in the NPC-treated animals along with suppressed immune populations. The differentiation profile of the exogenous NPCs and endogenous BrdU+ cells was location-dependent where GFP+ -rich areas drove undifferentiated phenotypes toward the oligodendrocyte lineage. In situ oligodendrocyte enrichment was demonstrated through increased (p < 0.001) gap junction channels of Cx32 and Cx47, reliable markers for proliferative oligodendroglia syncytium. TEM morphometric analysis ultimately manifested an increased g-ratio in lumbosacral fibers of the recovered animals (p < 0.001). Herein, we suggest that a single, lumbar intrathecal administration of NPCs capacitated a viable cellular load and resulted in clinical and pathological amelioration, stimulating resident OPCs to overcome the remyelination failure in EAE demyelinating locale.

Dataset Information

Swap70 promotes neural precursor cell cycle exit and oligodendrocyte formation.

Publications

swap70 promotes neural precursor cell cycle exit and oligodendrocyte formation.

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