Tgf-β-mediated FasL-Fas-caspase pathway is crucial during palatogenesis

Programmed cell death,or apoptosis,is one of the fates of the medial edge epithelium (mee) during palatal fusion. transforming growth factor β (tgf-β) signaling (such as tgf-β3) is required for the disappearance of the mee,but the relationship between tgf-β3 and apoptosis remains unclear. here we show that the fas ligand (fasl)-fas-caspase extrinsic apoptosis pathway functions during palatal fusion in wild-type mice,but is not detectable in mice lacking tgf-β3 (tgf-β3-/- ) or tgfβr2 in the mee (k14-cre;tgfbr2fl/fl). inhibition of the fasl-fas system results in persistence of the midline epithelial seam (mes) and inhibition of caspase activity during palatal organ culture. moreover,ectopic fasl protein induces apoptosis in mes of k14-cre;tgfbr2fl/fl mice. thus,we conclude that the fasl-fas-caspase extrinsic apoptosis pathway is regulated by the tgf-β3 signaling cascade and is essential for palatal fusion during craniofacial development. © 2011 international & american associations for dental research.