STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation.

Tubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

BACKGROUND: Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized. RESULTS: Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa-/- mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs. CONCLUSIONS: Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.

bFGF Protects Pre-oligodendrocytes from Oxygen/Glucose Deprivation Injury to Ameliorate Demyelination.

One of the pathological hallmarks of periventricular white matter injury is the vulnerability of pre-oligodendrocytes (preOLs) to hypoxia-ischemia (HI). There is increasing evidence that basic fibroblast growth factor (bFGF) is an important signaling molecule for neurogenesis and neuroprotection in the central nervous system. However, it is unknown whether bFGF protects preOLs from oxygen/glucose deprivation (OGD) damage in vitro and promotes remyelination in HI-induced rats. In this present study, bFGF exerted a protective effect on myelin by increasing the myelin thickness, the number of myelinated axons, and myelin basic protein expression in the HI-induced demyelinated neonatal rat corpus callosum. In vitro, bFGF ameliorated the impaired mitochondria and cell processes induced by OGD to promote the survival of isolated O4-positive preOLs. Additionally, the expression of fibroblast growth factor receptor 3 (FGFR3) was dramatically up-regulated in the preOLs after bFGF administration in vivo and in vitro. Thus, bFGF-stimulated remyelination in HI-induced rats by protecting the preOLs from hypoxic injury, and the mechanism involved may be mediated by FGFR3.

Olig2 overexpression accelerates the differentiation of mouse embryonic stem cells into oligodendrocyte progenitor cells in vitro.

Oligodendrocyte progenitor cells (OPCs) transplantation is receiving considerable attention in the field of regenerative medicine therapy for demyelinating diseases. Although embryonic stem cells (ESCs) have been successfully induced to differentiate into OPCs with cytokines cocktails in vitro, the regulatory roles of many key transcription factors in this process are not clear. Here, we introduced oligodendrocyte lineage transcription factor 2 (Olig2), a basic helix-loop-helix transcription factor, into mouse embryonic stem cells (mESCs) to investigate its effects on the differentiation of mESCs into OPCs. The results showed that Olig2 overexpression alone did not affect pluripotency of mESCs, but in the stimulation of differentiating cocktails, Olig2 accelerated mESCs to differentiate into OPCs, shortening the induction time span from normal 21 days to 11 days. Further study demonstrated the Olig2-mESCs derived OPCs were able to differentiate into C-type natriuretic peptid (CNP) and Myelin Basic Protein (MBP) positive mature oligodendrocytes (OLs) in vitro, suggesting these induced OPCs might be favorable for myelin regeneration in vivo.

Quercetin improves hypoxia-ischemia induced cognitive deficits via promoting remyelination in neonatal rat.

Myelination failure is associated with perinatal cerebral hypoxia-ischemia (PHI) induced brain injury in premature infants. How to efficiently promote remyelination is crucial for improving cognitive deficits caused by brain injury. Here, we demonstrated that quercetin (Que), a kind of flavonoids, significantly improved cognitive deficits and the behavior of PHI-rat in Morris water maze and open field tasks. After administration of Que to PHI-rat, the number of neogenetic Olig2⁺ oligodendrocyte progenitor cells (OPCs) was evidently increased in the subventricular zone. Additionally, in corpus callosum (CC), the expression of MBP (myelin basic protein) was increased, and the myelin sheaths reached normal level at 30 days with more compact while less damaged myelin sheaths and more mature oligodendrocytes (OLs) repopulating the CC compared with PHI groups. In a word, our findings indicated that Que could remarkably improve both cognition performance and myelination in the context of PHI-induced brain injury by promoting the proliferation of OPCs and strengthening survival of OLs in vivo.