ABSTRACT
How neuronal signaling affects brain myelination remains poorly understood. We show dysregulated neuronal RHEB-mTORC1-DLK1 axis impairs brain myelination. Neuronal Rheb cKO impairs oligodendrocyte differentiation/myelination, with activated neuronal expression of the imprinted gene Dlk1. Neuronal Dlk1 cKO ameliorates myelination deficit in neuronal Rheb cKO mice, indicating that activated neuronal Dlk1 expression contributes to impaired myelination caused by Rheb cKO. The effect of Rheb cKO on Dlk1 expression is mediated by mTORC1; neuronal mTor cKO and Raptor cKO and pharmacological inhibition of mTORC1 recapitulate elevated neuronal Dlk1 expression. We demonstrate that both a secreted form of DLK1 and a membrane-bound DLK1 inhibit the differentiation of cultured oligodendrocyte precursor cells into oligodendrocytes expressing myelin proteins. Finally, neuronal expression of Dlk1 in transgenic mice reduces the formation of mature oligodendrocytes and myelination. This study identifies Dlk1 as an inhibitor of oligodendrocyte myelination and a mechanism linking altered neuronal signaling with oligodendrocyte dysfunction.
Subject(s)
Myelin Sheath , Ras Homolog Enriched in Brain Protein , Signal Transduction , Animals , Mice , Cell Differentiation/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Mice, Transgenic , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Signal Transduction/physiology , Ras Homolog Enriched in Brain Protein/metabolismABSTRACT
Amino acids are essential for cell growth and metabolism. Amino acid and growth factor signaling pathways coordinately regulate the mechanistic target of rapamycin complex 1 (mTORC1) kinase in cell growth and organ development. While major components of amino acid signaling mechanisms have been identified, their biological functions in organ development are unclear. We aimed to understand the functions of the critically positioned amino acid signaling complex GAP activity towards Rags 2 (GATOR2) in brain development. GATOR2 mediates amino acid signaling to mTORC1 by directly linking the amino acid sensors for arginine and leucine to downstream signaling complexes. Now, we report a role of GATOR2 in oligodendrocyte myelination in postnatal brain development. We show that the disruption of GATOR2 complex by genetic deletion of meiosis regulator for oocyte development (Mios, encoding a component of GATOR2) selectively impairs the formation of myelinating oligodendrocytes, thus brain myelination, without apparent effects on the formation of neurons and astrocytes. The loss of Mios impairs cell cycle progression of oligodendrocyte precursor cells, leading to their reduced proliferation and differentiation. Mios deletion manifests a cell type-dependent effect on mTORC1 in the brain, with oligodendroglial mTORC1 selectively affected. However, the role of Mios/GATOR2 in oligodendrocyte formation and myelination involves mTORC1-independent function. This study suggests that GATOR2 coordinates amino acid and growth factor signaling to regulate oligodendrocyte myelination.
Subject(s)
Amino Acids/metabolism , Brain/metabolism , Multiprotein Complexes/metabolism , Myelin Sheath/metabolism , Signal Transduction , Animals , Cell Differentiation , Cell Lineage , Cell Proliferation , Gene Deletion , Mechanistic Target of Rapamycin Complex 1/metabolism , Mice, Knockout , Models, Biological , Neural Stem Cells/metabolism , Oligodendroglia/cytology , Oligodendroglia/metabolism , TransgenesABSTRACT
Two new species of Achipteriidae, Dentachipteria sidorchukae sp. nov. from moss and Cubachipteria clavata sp. nov. from soil in Yunnan Province, Southwest China are described and illustrated. Dentachipteria sidorchukae sp. nov. is most similar to Dentachipteria ringwoodensis but can be distinguished from the latter by the following characterstics: 3 or 4 pteromorphic denticles, seta in thickened, not reaching distal parts of lamellae. Cubachipteria clavata sp. nov. is most similar to Cubachipteria maxsellnicki, but can be distinguished from the latter by the following characterstics: seta in setiform, slightly barbed, not reaching distal parts of lamellae, seta le smooth, inserted ventrally on the lamellae.
Subject(s)
Bryophyta , Mites , Animals , ChinaABSTRACT
A new species, Pergalumna (Pergalumna) sidorchukae sp. nov., and two newly recorded species, Pergalumna (Pergalumna) jongkyui and Pergalumna (Pergalumna) amorpha, of oribatid mites of the subgenus Pergalumna (Pergalumna) from China, are described and illustrated in this study. The new species is similar to Pergalumna (Pergalumna) yurtaevi, but it differs from the latter by the surface of notogaster, the shape and size of notogastral porose areas, and the absence of postanal porose area.
Subject(s)
Fabaceae , Mites , Animals , ChinaABSTRACT
Two new species of oribatid mites of the subgenus Galumnella (Galumnella) (Acari: Oribatida: Galumnellidae) are described from soil and litter of forest zones of China. Galumnella (G.) nonporosa sp. nov. differs from Galumnella (G.) nipponica by the falciform bothridial setae and obvious reticulate pattern in the anogenital region. Galumnella (G.) sidorchukae sp. nov. differs from Galumnella (G.) cellularis by the laciniate bothridial setae and by the absence of postanal porose area. Morphological additions to the description of Galumnella (G.) parageographica are presented based on Chinese specimens, which is recorded in China for the first time.
Subject(s)
Mites , Animals , China , Forests , SoilABSTRACT
Two new species of Lohmanniidae, Papillacarus (Papillacarus) retinervius sp. nov. from soil in Hainan Province, South China and Papillacarus (Papillacarus) mammilatus sp. nov. from moss and soil in Guizhou Province, Southwest China are described and illustrated. Papillacarus (P.) retinervius sp. nov. is most similar to Papillacarus (P.) polygonatus (Ermilov Anichkin, 2011), however, it can be distinguished from the latter by the following characterstics: 20-21 pairs of additional neotrichal setae, setae d2, e2, h1, p1 shorter, as long as d1, epimeral setal formula 10-8-4-3. Papillacarus (P.) mammilatus sp. nov. is most similar to Papillacarus (P.) angulatus (Wallwork, 1962), however, it can be distinguished from the latter by the following characterstics: transverse bands S3 complete, eight pairs of subcapitular setae, epimeral setal formula 10-6-3-4.
