Dorsal cell rearrangements in Caenorhabditis elegans require the zinc finger protein DIE-1

The mechanism by which epithelial cells undergo directed rearrangement is central to epithelial morphogenesis, yet the regulation of these movements remains poorly understood. We have investigated epithelial cell rearrangement (intercalation) in the dorsal hypodermis of the C. elegans embryo by analyzing the die-1 mutant, which fails to undergo normal intercalation.; Dorsal hypodermal cells of die-1(w34) homozygous embryos appear to initiate but fail to complete the process of intercalation. Despite abnormal intercalation the subsequent morphogenetic movements that enclose the embryo with epithelial cells, and the process of dorsal cell fusion still occur, albeit aberrantly. Elongation of the embryo into a worm-like shape is disrupted in die-1 embryos, suggesting that the process of intercalation may be necessary for the subsequent elongation of the embryo. Phalloidin staining shows that actin filaments are not properly organized within the dorsal hypodermis of die-1 embryos, consistent with a requirement for intercalation in the subsequent elongation of the embryo. DIE-I is also required for morphogenesis of the pharynx and for the organization of body muscle. Laser ablation of muscle cells indicates that intercalation can occur independently of interactions with the underlying muscle tissue.; The die-1 gene encodes an apparent C2H2 zinc finger protein containing four fingers, and likely acts as a transcription factor. Immunostaining with DIE-1 polyclonal antibodies and expression of a DEE-1-GFP translational fusion protein indicate DIE-1 is present in the nuclei of hypodermal, muscle, and pharyngeal cells and suggests that DIE-1 acts independently in each of these tissues to regulate morphogenetic movements. Mosaic analysis indicates that absence of DIE-1 in specific portions of the dorsal hypodermis affects intercalation only within the cells that fail to express DIE-1.; This is the first analysis of an intercalation defective mutant in C. elegans and provides the first evidence that intercalation is required for subsequent morphogenetic events during embryonic development. We propose a model in which intercalation is necessary for the subsequent elongation of the embryo and discuss mechanisms by which DIE-1 may regulate the movements of intercalation as well as other morphogenetic events during embryogenesis.