Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development.DOI: http://dx.doi.org/10.7554/eLife.13273.001

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects.

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Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.

Highlights d Surface ectoderm cells adhere at the fusion site via integrin b1 focal clustering d Integrins mediate junction shortening and formation of a semi-rosette structure d This configuration enables juxtaposition across the midline for fusion propagation d Tissue-specific ablation of integrin b1 prevents zippering, causing spina bifida

Titanium phosphate supported in a mixed oxide matrix was prepared by reacting SiO 2 / TiO 2 , obtained from the sol-gel process, with phosphoric acid. HPO 4 2-is the species present in the matrix, and it is immobilized by the Ti-O-P bond on the surface. The titanium phosphate is highly and homogeneously dispersed in the SiO 2 /TiO 2 matrix, with the domain of titanium oxide particles about 1 nm, estimated from the UV absorption band threshold. The specific surface areas, determined by the BET multipoint method, changed between 397 and 755 m 2 g -1 and the average pore volumes between 0.38 and 0.63 mL g -1 for samples prepared with different contents of titanium phosphate. The titanium hydrogenphosphate is thermally very stable and showed a high proton exchange capacity between 0.50 and 1.10 mmol g -1 .

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