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
External Project ID:NSC100-2314-B182-043
Status | Finished |
---|---|
Effective start/end date | 01/08/11 → 31/07/12 |
Keywords
- Interferon regulatory factor 6 (IRF6)
- Transforming growth factor beta3 (TGFB3)
- cleft palate
- lentivirus
- RNA interference (RNAi)
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.