Coordinated control of oligodendrocyte development by extrinsic and intrinsic signaling cues

Oligodendrocytes, the myelin-forming cells for axon ensheathment in the central nervous system, are critical for maximizing and maintaining the conduction velocity of nerve impulses and proper brain function. Demyeli- nation caused by injury or disease together with failure of myelin regeneration disrupts the rapid propagation of action potentials along nerve fibers, and is associated with acquired and inherited disorders, including dev- astating multiple sclerosis and leukodystrophies. The molecular mechanisms of oligodendrocyte myelination and remyelination remain poorly understood. Recently, a series of signaling pathways including Shh, Notch, BMP and Wnt signaling and their intracellular effectors such as Olig1/2, Hesl/5, Smads and TCFs, have been shown to play important roles in regulating oligodendrocyte development and myelination. In this review, we summarize our recent understanding of how these signaling pathways modulate the progression of oligoden- drocyte specification and differentiation in a spatiotemporally-specific manner. A better understanding of the complex but coordinated function of extracellular signals and intracellular determinants during oligodendrocyte development will help to devise effective strategies to promote myelin repair for patients with demyelinating diseases.

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF.