INTRODUCTION During embryonic development of many organisms, the movement and folding of epithelial layers give rise to a variety of tissues and organs. Epithelial invagination is a morphogenetic movement by which the epithelium folds

During embryonic development of many organisms, the movement and folding of epithelial layers give rise to a variety of tissues and organs. Epithelial invagination is a morphogenetic movement by which the epithelium folds inward through a process involving individual cell shape changes (reviewed by Ettensohn, 1985; Fristrom, 1988). Several general models have been proposed to explain how an epithelium invaginates. In the apical constriction model, nuclei migrate to a more basal position and the apical membranes constrict, thus turning a columnar cell into a wedge-shaped one. Changes in the underlying microfilament and microtubule systems are thought to drive this change in cell shape (reviewed by Ettensohn, 1985; Messier, 1978). In the second model for invagination, changes in cell-cell adhesion are proposed to drive internalization (Gustafson and Wolpert, 1962; Nardi, 1981; Mittenthal and Mazo, 1983). If an increase in adhesion between cells of an invaginating epithelium results in increased cell height while leaving the basal surface adherent to the substratum, the apical surface area would decrease, causing the epithelium to fold inward. During invagination of the mesodermal primordia in Drosophila embryos, changes in the location, size and morphology of the cadherinand cateninbased adhesion junctions are associated with changes in the shape and internalization of the cells (Oda et al., 1998), supporting the cell-cell adhesion model for invagination. In the third model, changes in the extracellular matrix (ECM) are proposed to drive invagination (Lane et al., 1993). In gastrulating sea urchin embryos, invaginating cells are proposed to deposit a new hygroscopic layer of ECM between their apical surfaces and the older less hygroscopic layer. The new, more hygroscopic layer of ECM swells and increases in surface area due to its greater hydration, thus driving the bilayered ECM and underlying epithelial sheet to bend inward. Recent studies on epithelial invagination in genetically manipulatable organisms, such as C. elegans and D. melanogaster, have begun to identify mutations that affect invagination. A screen for mutations affecting vulval invagination in C. elegans identified the squashed vulva (sqv) genes that most likely encode components of a conserved glycosylation pathway (Herman et al., 1999; Herman and Horvitz, 1999). In sqv mutants, the vulval invagination partially collapses, resulting in a reduced invagination space (Herman et al., 1999). The sqv genes are proposed to establish and/or maintain the rigidity of the invaginating vulval epithelium. The collapsed phenotype could be either due to defects in adhesion between the invaginating cells or, perhaps more likely, due to defects in the rigidity of the ECM that lines the invaginating space. In the gastrulating Drosophila embryo, epithelial invagination occurs during the internalization of the 4217 Development 127, 4217-4226 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV8755