Effect of IRF6 Gene Silence on the Cellular Polarity of Peridermin Palatal Morphogenesis

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Cleft lip with or without cleft palate (CLP) could cause significant functional and aesthetic deformity, and bring psychosocial burden to patients and family. Although good treatment results have been achieved in Taiwan, molecular study for prenatal prevention and management has not yet been compatible. Recently, Interferon regulator factor 6 (IRF6) gene was found to be associated with the formation of CLP. Mutation of IRF6 was observed in 12% of patients with CLP, and this rate could increase when new mutation loci are discovered. Therefore, IRF6 gene may become a potential target gene for prenatal manipulation. However, its cellular and molecular mechanisms are still unclear. The effect of IRF6 gene silence on the fusion of mouse embryonic palatal shelves was studied in our previous works. In vitro palatal shelf organ culture model has been established, and the functioning clone of IRF6-ShRNA has been tested successfully and transfected into the palatal tissues. It was found that IRF6 gene silence does not interfere with in vitro embryonic palatal fusion in our experiment. We hypothesize that IRF6 gene may exert indirect function onto the palatal fusion process. Periderm is a layer of flat cells covering the palatal shelves during the palatal development. Several published studies showed that the integrity of cellular polarity of the palatal periderm cells might play an important role in palatal epithelia growth, tissue remodeling, adhesion and fusion of the palatal shelves in the palatal development. Aberrant adhesions between the palatal epidermis and intra-oral tissues were observed in IRF6 knock-down mice. With these background findings, we wish to set up in vitro palate-tongue organ culture model, using CD15 molecule as marker to evaluate the periderm cells, to observe the expression of survival protein-Survivin, death receptor-Bax, cellular migration “on and off” molecule-Cdc42 and the tight junction protein-Occludin during the palatal development. Furthermore, we will use lentivirus-IRF6 ShRNA to transfect the periderm cells,in order to observe the impact of IRF6 gene silence on the polarity of periderm cell and the expression of the above molecules, and finally to elucidate the functional mechanism of IRF6 in palatogenesis. This study should be able to provide molecular evidence for IRF6 as a target gene for possible prenatal management of CLP in the future.

Project IDs

Project ID:PC10007-0348
External Project ID:NSC100-2314-B182-043
StatusFinished
Effective start/end date01/08/1131/07/12

Keywords

  • Interferon regulatory factor 6 (IRF6)
  • Transforming growth factor beta3 (TGFB3)
  • cleft palate
  • lentivirus
  • RNA interference (RNAi)

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