YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction.

[Evaluation of the use of ultrasonic hand piece and micro-invasive tips in children's dental caries therapy].

OBJECTIVE: To assess the effect and efficacy of an ultrasonic hand piece and micro-invasive tips in removal of carious lesion, as well as the pediatric patients' feedback of this device in comparison to the conventional one. METHODS: Seventy-two pediatric patients aged 3 to 12 were recruited in the study. Each patient had at least two carious lesions bilaterally in the same arch, one tooth was assigned to be treated with ultrasonic hand piece and micro -invasive tips (MIT) while the contra lateral side was treated with conventional hand piece. The effect and efficacy of MIT was determined by the appearance of the color and texture of the teeth, the patient's reaction during the treatment, and the pain scale level. Postoperative sensitivity, restoration and plaque score were also recorded in the follow-up visit after six months. The result was evaluated with SPSS 14.0 statistic software Wilcoxon Signed Ranks Test and t-test. RESULTS: The average treatment time of the experimental group was 4 minutes; and that of the control group 3 minutes and 34 seconds (P<0.05), which was a clinically significant difference. Both methods were effective in removing carious lesion. In comparison to the patient anxiety and cooperation, the scores of the experimental group were fewer than those of the control group, which was also a clinically significant difference. In the experimental group, 89.2% of the patients felt comfortable or slightly uncomfortable, while 73.1% of the patients did in the control group. In the 6-month follow-up study, 1 treated tooth from the experimental group had sensitivity, while 4 treated teeth from the control group had sensitivity. And 88.2% of the pediatric patients expressed that they were more willing to be treated with ultrasonic hand piece and micro-invasive tips. CONCLUSION: Ultrasonic hand piece and micro-invasive tips is equally effective in removing carious lesion like the conventional hand piece. SONICFlex has reduced noise level, and made the operation more precise with less pulp sensitivity, and thus is more acceptable to pediatric patients.