The question of whether Fe­(IV) or SO4 •– is the dominant intermediate in the Fe­(II)-activated peroxydisulfate process [Fe­(II)/PDS process] remains unanswered. In this study, besides Fe­(IV), SO4 •– and HO• were shown to be produced in the Fe­(II)/PDS process by using multiple probes [dimethyl sulfoxide, methyl phenyl sulfoxide, p-nitrobenzoic acid (p-NBA), and benzoic acid (BA)]. The removal of p-NBA and BA and the influence of BA on the yield of methyl phenyl sulfone (PMSO2) indicated that the major oxidizing intermediate changed from Fe­(IV) to SO4 •–/HO• with an increase in the PDS/Fe­(II) molar ratio at pH 3.0. Fe­(IV), SO4 •–, and HO• were all involved in this process at pH 3.0–6.5, but their available amounts that contributed to abating organic contaminants decreased with an increase in pH considering the influence of pH on the generation of PMSO2 and p-hydroxybenzoic acid. Furthermore, Fe­(IV), SO4 •–, and HO• contributed differently to abating different organic contaminants because of the different reactivities of these oxidizing oxidants toward different organic contaminants. Overall, this study demonstrates that multiple oxidizing species [Fe­(IV), SO4 •–, and HO•] are generated in the Fe­(II)/PDS process, which was significant for the application of this process and understanding the mechanisms of Fe­(II)-activated peroxide processes.

Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show that 3D mesenchymal cell intercalations are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor that we knock-in to the mouse genome, we show that cortical force oscillations promote these intercalations. Genetic loss- and gain-of-function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity and cytoskeletal oscillation. These processes diminish tissue rigidity and help cells to overcome the energy barrier to intercalation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a -mediated actomyosin polarity and cytosolic calcium transients that orient and drive mesenchymal cell intercalations. These findings advance our understanding of how developmental pathways regulate biophysical properties and forces to shape a solid organ primordium.

Graphical Abstract Highlights d Sufu exerts tumor-promoting and -suppressive functions in SHH medulloblastoma d Sufu;Spop double knockout medulloblastoma mouse model unveils GLI2 targetome d ATOH1 and GLI2 cooperate to activate target genes in SHH medulloblastoma SUMMARY SUFU alterations are common in human Sonic Hedgehog (SHH) subgroup medulloblastoma (MB). However, its tumorigenic mechanisms have remained elusive. Here, we report that loss of Sufu alone is unable to induce MB formation in mice, due to insufficient Gli2 activation. Simultaneous loss of Spop, an E3 ubiquitin ligase targeting Gli2, restores robust Gli2 activation and induces rapid MB formation in Sufu knockout background. We also demonstrated a tumor-promoting role of Sufu in Smo-activated MB ($60% of human SHH MB) by maintaining robust Gli activity. Having established Gli2 activation as a key driver of SHH MB, we report a comprehensive analysis of its targetome. Furthermore, we identified Atoh1 as a target and molecular accomplice of Gli2 that activates core SHH MB signature genes in a synergistic manner. Overall, our work establishes the dual role of SUFU in SHH MB and provides mechanistic insights into transcriptional regulation underlying Gli2-mediated SHH MB tumorigenesis. (C) Survival is normal in Sufu KO mice, while Ptch1 KO mice rapidly succumb to MBs. (D) Gene expression profiling by cDNA microarray reveals downregulation of several Gli target genes and moderate expression of some Hh pathway components and MB signature genes in Sufu KO cerebellum at P13, while Ptch1 KO MBs displays upregulation of Hh component genes and full-blown MB signature. See also Figure S1.