title: The pivotal role of CCN2 in mammalian palatogenesis.
abstract: Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis. Similar to previously published reports, the absence of CCN2 inhibits proliferation of cells in the palate specifically at the G1/S transition. Absence of CCN2 also inhibited palatal shelf elevation from the vertical to horizontal position. CCN2 KO mesenchymal cells demonstrated deficiencies in adhesion and spreading owing to an inability to activate Rac1 and RhoA. On the contrary, CCN2 KO mesenchymal cells exhibited increased rates of migration compared to WT cells. The addition of exogenous CCN2 to KO mesenchymal cells restored their ability to spread normally on fibronectin. Finally, utilizing an organ culture model we show that the palatal shelves of the CCN2 KO mice demonstrate an inability to fuse when apposed. Together, these data signify that CCN2 plays an indispensible role in normal development of the mammalian palate and warrants additional studies to determine the precise mechanism(s) responsible for these effects.
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tarr
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Visser
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Moon
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA.
authors.forename: Honey
authors.initials: H
authors.lastname: Hendesi
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Barbe
authors.affiliation: Department of General Surgery, Division of Plastic and Reconstructive Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Bradley
authors.affiliation: Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad St. Suite 440, Philadelphia, PA, 19140, USA. spopoff@temple.edu.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Popoff
keywords: CCN2; Cranial neural crest; Palate elevation; Palate fusion; Palatogenesis; Proliferation