Drosophila peripodial cells, more than meets the eye? Matthew C. Gibson and Gerold Schubiger* Summary Drosophila imaginal discs (appendage primordia) have proved invaluable for deciphering cellular and molecular mechanisms of animal development. By combining the accessibility of the discs with the genetic tractability of the fruit fly, researchers have discovered key mechan- isms of growth control, pattern formation and long-range signaling. One of the principal experimental attractions of discs is their anatomical simplicity Ð they have long been considered to be cellular monolayers. During larval stages, however, the growing discs are 2-sided sacs composed of a columnar epithelium on one side and a squamous `peripodial' epithelium on the other. Recent studies suggest important roles for peripodial epithelia in processes previously assumed to be confined to colum- nar cell monolayers. BioEssays 23:691±697, 2001. ß 2001 John Wiley & Sons, Inc. Introduction In most primitive insect groups, the appendage primordia arise as evaginations or buds on the outside of the developing embryo. It is only in the more-derived holometabolous species, such as Drosophila, that some or all of the primordia of adult structures are sequestered in epidermal invaginations called imaginal discs. In Drosophila larvae, imaginal discs are flattened epithelial sacs with two opposing surfaces, a columnar epithelium and a squamous peripodial epithelium (or peripodial membrane). (1) Since the first disc fate maps were produced (2) and through to the molecular genetic dissections of the present day, investigations of disc develop- ment have focused on the more numerous cells of the columnar epithelium. Reasons for this emphasis are several. The thickened and opaque disc columnar epithelia are much more easily visible than the squamous peripodial sheet. More importantly, during metamorphosis, disc columnar cells directly produce the vast majority of the adult cuticle while peripodial cells make only a trifling contribution. As a result of these and other factors, Drosophila imaginal discs are often described as monolayered columnar epithelia. Although the peripodial and columnar epithelia literally constitute a contiguous cell sheet, the term monolayer does not accurately reflect the sac-like anatomy of the imaginal discs. Here we consider the often-ignored (and poorly named) peripodial `membranes'. Might their function extend beyond that of simple sheaths to contain developing discs? It has been known for some time that peripodial cells function in metamorphosis, (3,4) but more recent studies indicate that they could also regulate earlier phases of disc development. In reviewing the existing literature concerning the function of peripodial cells, we will advance the hypothesis that, despite a minimal direct contribution to the adult fly, peripodial cells figure prominently in larval and metamorphic development. For the purposes of this review, the term peripodial epithelium will be used in place of the historical but misleading designation peripodial membrane. We recommend that this change in nomenclature apply generally to future work with imaginal discs and note that `peripodial epithelium' is already the standard designation employed by the `Flybase' online Drosophila database. (5) Our discussion begins with adult morphogenesis at the onset of metamorphosis, where peripodial epithelia have a reasonably well-defined function. Imaginal discs develop internally in the larva and, during metamorphosis, a radical morphogenic transition externalizes the discs and assembles the adult de novo. During this stage, discs evert from within their peripodial sacs ( disc eversion) and then fuse with adjacent disc derivatives ( disc fusion) to form a continuous adult epidermis. (6) While some insightful older studies have considered the mechanisms of disc eversion, (3,4,6,7) more recent work has brought to light some of the cellular and molecular events underlying disc fusion. (8±10) Peripodial cells play crucial roles in both processes. Disc eversion Metamorphic events in Drosophila imaginal discs have been reviewed in detail. (6) In the mid-third instar, the steroid molting hormone 20E (hereafter referred to as ecdysone) induces the discs to undergo a series of complex metamorphic changes, generally termed evagination. Evagination involves two discrete processes: elongation, during which morphogenetic events in disc columnar epithelia cause lengthening and shaping of the appendages themselves, and eversion (Fig. 1A±D), wherein contraction of peripodial epithelia is thought to drive movement of the appendage to the outside of the larval epidermis. (6) As eversion occurs almost simulta- neously in all discs, it could be assumed to be globally BioEssays 23:691±697, ß 2001 John Wiley & Sons, Inc. BioEssays 23.8 691 Department of Zoology, University of Washington. Funding agency: The NIGMS (Grant number GM 07270). Ã Correspondence to: Gerold Schubiger, Department of Zoology, University of Washington, Seattle WA 98195. Review articles