RT Journal Article
SR Electronic
T1 Anterior Cleft Palate due to Cbfb deficiency and its rescue by folic acid
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 515650
DO 10.1101/515650
A1 Safiye E. Sarper
A1 Toshihiro Inubushi
A1 Hiroshi Kurosaka
A1 Hitomi Ono Minagi
A1 Yuka Murata
A1 Koh-ichi Kuremoto
A1 Takayoshi Sakai
A1 Ichiro Taniuchi
A1 Takashi Yamashiro
YR 2019
UL http://biorxiv.org/content/early/2019/01/09/515650.abstract
AB Core binding factor β (Cbfb) is a cofactor of Runx transcription factors. Among Runx transcription factors, Runx1 is a prerequisite for anterior-specific palatal fusion. However, whether Cbfb serves as a modulator or obligatory factor in Runx signaling that regulates palatogenesis is unclear. We herein report that Cbfb is essential and indispensable in anterior palatogenesis. Palatal fusion in Cbfb mutants is disturbed due to failed disintegration of the fusing epithelium specifically at the anterior portion, as is observed in Runx1 mutants. In this mutants, the Tgfb3 expression is disturbed at the corresponding area of the failed palatal fusion, where phosphorylation of Stat3 is also disturbed. TGFB3 protein rescues the palatal fusion in vitro. Strikingly, the anterior cleft palate in Cbfb mutants is further rescued by pharmaceutical application of folic acid that activates suppressed Stat3 phosphorylation and Tgfb3 expression in vitro. With these findings, we provide the first evidence that Cbfb is a prerequisite for anterior palatogenesis as an obligatory cofactor in the Runx1/Cbfb-Stat3-Tgfb3 signaling axis. Furthermore, the rescue of the mutant cleft palate using folic acid may elucidate potential therapeutic targets by Stat3 modification for the prevention and pharmaceutical intervention of cleft palate.Summary Statement Epithelial deletion of Cbfb results in an anterior cleft palate with impaired fusion of the palatal process and folic acid application rescues the mutant phenotype with Stat3 activation in vitro.