Epithelial Invagination: Adhesive Properties of Cells Can Govern Position and Directionality of Epithelial Folding

Definitive embryonic forms emerge during animal development as epithelial cell layers repeatedly fold and interact. Inductive influences of adjacent cells specify sites of folding in epithelia. The cellular properties that are altered by induction result in characteristic changes in cell form which accompany folding. The ubiquitous presence of microfilaments and microtubules in cells undergoing invagination has led to the belief that cytoskeletal elements are the causal agents for epithelial folding. Most of the research emphasizing the importance of cytoskeletal elements is based on the use of anticytoskeletal drugs and the premise that these drugs specifically disrupt the architecture of the cytoskeleton. Numerous experiments, however, have shown that these drugs do not exert their effects solely on the cytoskeleton. They also affect cell surface properties. The possibility that localized increases in cell surface adhesivity can orchestrate cellular form changes and subsequent folding movements has been repeatedly considered for theoretical reasons, but rarely tested in the laboratory. The recent finding that invagination or evagination of an epithelial monolayer can be induced following transposition of grafts between proximal and distal extremes of the moth pupal wing has provided new support for this idea. Adhesive properties of wing cells are graded along the proximo-distal axis of the wing, and the direction of induced epithelial folding is related to relative adhesiveness of graft and host cells. Graft invagination only occurs following a transfer of tissue from proximal extreme to distal extreme, whereas graft evagination only accompanies the reciprocal exchange of tissues. Emphasis on the role of cytoskeletal elements in governing the folding of epithelia should be tempered by an appreciation of the importance of cell adhesivity. The observed accumulation of cell surface molecules at sites destined to invaginate may contribute to increased adhesivity of the invaginating population of cells, and oriented microtubules and microfilaments may simply stabilize the cellular configurations assumed as cell surface properties drive changes in cellular form.