Journal of Clinical Toxicology
Open Access

Genetic dissection of signaling network during mammalian secondary palate development and cleft palate

4^th Global Summit on Toxicology

August 24-26, 2015 Philadelphia, USA

Jixiang Ding

Posters-Accepted Abstracts: J Clin Toxicol

Abstract :

Cleft palate is a common birth defect that affects approximately 1:700 births. Palate formation during embryonic development is a
complex process involving a series of steps such as vertical growth of palate shelf, palate re-orientation or elevation to horizontal
level and horizontal growth until meet and fusion along the facial midline. Each step is under strict regulation to avoid possible
developmental disruption and cleft palate. In this study, we used genetic approaches to investigate the functions and interactions of
major signaling pathways during mouse secondary palate development and cleft palate. Zeb1 encodes a transcription modulator that
regulates the activities of SHH and TGF-βsignaling pathways. Genetic inactivation of the Zeb1 gene causes cleft palate due to delayed
palate re-orientation/elevation. By examining the re-orientation process in Zeb1 mutant line, we found that palate re-orientation is
initiated by cell migration and outgrowth from the side of vertical palate shelf. Considering the critical role of FGFs in controlling
embryonic cell migration and movement, we investigated the function of FGF8 in palate re-orientation by tissue specific deletion
of Fgf8 gene in palate mesenchymal cells and disclosed varied cleft palate phenotype associated with defects in palate re-orientation
including vertical palate and shortened horizontal palate. In addition, we found that FGF8 carries out its role in palate development
by interacting with WNT, another important signaling pathway. Since ZEB1 is a TGF-β modulator, we re-visited the issue of TGF-β1,
2 in palate and found that Tgf-β1 and Tgf-β2 double mutants display cleft palates in strain dependent manner.