Title:Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfβ3<sup>-/-</sup> Mouse Fetuses
VOLUME: 4 ISSUE: 1
Author(s):Dennis Warner, Jixiang Ding, Partha Mukhopadhyay, Guy Brock, Irina A. Smolenkova, Ratnam S. Seelan, Cindy L. Webb, James L. Wittliff, Robert M. Greene and M. Michele Pisano
Affiliation:Department of Molecular, Cellular, and Craniofacial Biology, University of Louisville Birth Defects Center, 501 S. Preston St, suite 350, University of Louisville, Louisville, Kentucky, 40202, USA.
Keywords:Embryo, medial edge epithelium, mesenchymal, microRNA, palate, TGF-β3.
Abstract:Clefting of the secondary palate is the most common birth defect in humans. Midline fusion
of the bilateral palatal processes is thought to involve apoptosis, epithelial to mesenchymal transition,
and cell migration of the medial edge epithelium (MEE), the specialized cells of the palate that mediate
fusion of the palatal processes during fetal development. Data presented in this manuscript are the
result of analyses designed to identify microRNAs that are expressed and regulated by TGFβ3 in developing
palatal MEE. The expression of 7 microRNAs was downregulated and 1 upregulated in isolated MEE from wildtype
murine fetuses on gestational day (GD) 13.5 to GD14.5 (prior to and during epithelial fusion of the palatal processes,
respectively). Among this group were miRNAs linked to apoptosis (miR-378) and epithelial to mesenchymal transformation
(miR-200b, miR-205, and miR-93). Tgfβ3-/- fetuses, which present with a complete and isolated cleft of the secondary
palate, exhibited marked dysregulation of distinct miRNAs both in the palatal MEE and mesenchyme when compared to
comparable wild-type tissue. These included, among others, miRNAs known to affect apoptosis (miR-206 and miR-186).
Dysregulation of miRNAs in the mesenchyme underlying the palatal MEE of Tgfβ3-/- fetuses is also discussed in relation
to epithelial-mesenchymal transformation of the MEE. These results are the first systematic analysis of the expression of
microRNAs in isolated fetal palatal epithelium and mesenchyme. Moreover, analysis of the Tgfβ3 knockout mouse model
has enabled identification of miRNAs with altered expression that may contribute to the cleft palate phenotype.
