Programmed Cell Death and Cell Transformation in Craniofacial Development

Abstract

Fusion of branchial arch derivatives is an essential component in the development of craniofacial structures. Bilaterally symmetric branchial arch processes fuse in the midline to form the mandible, lips, and palate. The mechanism for fusion requires several different morphologic and molecular events prior to the completion of the mesenchymal continuity between opposing tissue processes. The ectodermal covering of the branchial arches is one of the cell types that has an important role during craniofacial development. The surface epithelia provide the initial adherence between the processes; however, this population of cells is ultimately absent from the fusion zone. The medial edge epithelium of the secondary palatal shelves is one example of such an epithelium that must disappear from the fusion zone of the secondary palate during development in order to complete palatal fusion. The mechanisms for removal of the epithelial cells from the fusion zone could include either programmed cell death, epithelial-mesenchymal transformation, or migration to adjacent epithelia. All three of these fates have been hypothesized as a mechanism for the removal of the palatal medial edge epithelia. The processes of programmed cell death, epithelial-mesenchymal transformation, and epithelial migration are reviewed with respect to both palatal fusion and results reported in other model systems.

TGF‐β3–dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion

“…One is the fate of MEE (Shuler, 1995) and the other is the requirement for TGF-␤3 (Kaartinen et al, 1995;Proetzel et al, 1995). Previous studies suggested that the specific effects of TGF-␤3 in MEE were controlled by T␤R-III modulating the access of TGF-␤ ligands to signaling receptors (Cui and Shuler, 2000).…”

“…The MEE from opposing sides contact in the midline and form an epithelial seam when the paired palatal shelves are approximated. As palatal fusion proceeds, the MEE seam quickly breaks down and ultimately the epithelial cells disappear from the midline (Shuler, 1995). It has been demonstrated that there are three distinct fates for MEE, which include epithelial-mesenchymal transformation (Shuler et al, 1991(Shuler et al, , 1992Griffith and Hay, 1992;Martinez-Á lvarez et al, 2000), migration (Carette and Ferguson, 1992), and programmed cell death (Mori et al, 1994;Martinez-Á lvarez et al, 2000).…”

Recent advances in craniofacial morphogenesis

“…7). The palatal structures are composed of the CNC-derived ectomesenchyme and pharyngeal ectoderm (Ferguson, 1988;Shuler, 1995). The epithelia that cover the palatal shelves are regionally divided into oral, nasal, and medial edge epithelium (Fig.…”

Programmed cell death is not a necessary prerequisite for fusion of the fetal mouse palate.

“…The formation of the secondary palate in mammalian fetuses involves a series of developmental events that occur in a spatially and temporally coordinated manner (Ferguson, 1988;Hay, 1995;Shuler, 1995). Opposing bilateral palatal shelves elevate horizontally, grow medially and finally fuse with each other in the midline.…”