Identification for TGF-beta signaling during palatal development

调控腭裂发生的分子机制仍不完全，但最有可能参与腭裂的分子病因学。目的是研究TGF-β 3 II型和III型受体（TβR-II/III）被敲低后在体外培养的NIH 3 T3细胞系和腭器官中的信号转导。用siTβR-II/III处理降低了靶基因的表达。E13+ 72 h，TβR-II/III被敲除时，治疗的上颚部分融合，而所有对照上颚均完全融合。在siTβR-II/III处理的NIH 3 T3细胞和腭突中，下游基因表达减少。目前的研究表明，敲除TβR-II和III可以通过降低磷酸化Smad 2的水平来影响TGF-β下游信号通路。siTβR-II/III治疗导致持续的腭突细胞增殖，这已被证明与未能完成腭融合事件有关。

The molecular mechanisms regulating palatogenesis remain incompletely characterized but are most likely to be involved in the molecular etiology for cleft palate. The objective was to investigate TGF-β3 signaling when both TGF-β type II and III receptors (TβR-II/III) were knocked down an NIH3T3 cell line and palatal organ culture in vitro. Treatment with siTβR-II/III reduced the expression of the target genes. The treated palates were partially fused at E13+72h when TβR-II/III were knocked down,although all control palate were completely fused. The downstream genes was decreased in the siTβR-II/III treated NIH3T3 cells and palatal shelves. The present study demonstrated that knocking down both TβR-II and III could affect the downstream signaling pathway of TGF-β by reducing the levels of phospho-Smad2. The siTβR-II/III treatment resulted in persistent MEE cell proliferation, which has been shown to be linked to a failure to complete palatal fusion events.