Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans.

neural tube defects (NTDs) are severe malformations of the central nervous system caused by genetic and environmental factors is complex. Among Ovine Clia Kitshe genes involved in neural tube cilia-related genes has been well defined and found to be essential for the completion of the closure of the neural tube (NTC). 

We have done a generation sequencing of target genes in 373 NTDs and 222 healthy controls, and found eight of certain diseases rare mutation in a gene related to cilia-DNAAF1 DNAAF1 play a central role in the cytoplasm preassembly of different complex dynein-arm, and is expressed in several tissues key involved in the development of the nervous system, such as neural tube, plate floor, knot embryos, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and function mutations in DNAAF1 in cells transfected to analyze the relationship between the potential of this mutant for NTDs in humans. 

One rare frameshift mutation (p.Gln341Argfs * 10) resulted in DNAAF1 protein expression was significantly reduced, compared with the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic dynein complex preassembly-arm in cellular assay. Furthermore, the results of NanoString assay on mRNA samples showed that mutant DNAAF1 NTD change the level of gene expression related NTC. Overall, these findings suggest that a rare mutation in DNAAF1 can contribute to susceptibility to NTDs in humans.

Resveratrol protects the integrity of the primary cilia of human mesenchymal stem cells from cigarette smoke increases the osteogenic differentiation in vitro.

Few studies have examined the negative effects of cigarette smoke on bone healing; However, the complex pathogenesis remains unclear. One of the major determining factors important and effective fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSC) into bone-forming cells. More recently, the primary cilia, sensory organelles microtubule-based, have proven to be important in the commitment and differentiation of MSCs descent. 

Our present study shows that exposure to cigarette smoke extract (CSE 0.1-10%) interference osteogenic differentiation of human mesenchymal stem cell Porcine Clia Kits line (SCP-1) and attractive, it also affects the distribution of primary cilia and integrity in these cells during differentiation. Furthermore, a large number of free radicals produced by the CSE could be the cause of the loss of primary cilia ever since treatment with 0.01% of hydrogen peroxide, a free radical premiered at CSE, destroying the primary cilia in these cells. weak differentiation of CSE exposure to SCP-1 cells was also correlated with significantly reduced expression of transcription factors and target genes specifically primary cilia hedgehog signaling, a key player in osteogenic differentiation.