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The Stubble-stubbloid (Sb-sbd) gene is required for hormone-dependent epithelial morphogenesis of imaginal discs of Drosophila, including the formation of bristles, legs, and wings. The gene has been cloned by using Sb-sbd-associated DNA lesions in a 20-kilobase (kb) region of a 263-kb genomic walk. The region specifies an -3.8-kb transcript that is induced by the steroid hormone 20-hydroxyecdysone in imaginal discs cultured in vitro. The conceptually translated protein is an apparent 786-residue type II transmembrane protein (N terminus in, C terminus out), including an intracellular N-terminal domain of at least 35 residues and an extracellular C-terminal trypsin-like serine protease domain of 244 residues. Sequence analyses indicate that the Sb-sbd-encoded protease could activate itself by proteolytic cleavage. Consistent with the cell-autonomous nature of the Sb-sbd bristle phenotype, a disulfide bond between cysteine residues in the noncatalytic N-terminal fragment and the C-terminal catalytic fragment could tether the protease to the membrane after activation. Both dominant Sb and recessive sbd mutations affect the organization of microfilament bundles during bristle morphogenesis. We propose that the Sb-sbd product has a dual function. (i) It acts through its proteolytic extraceliular domain to detach imaginal disc cells from extracellular matrices, and (it) it transmits an outside-to-inside signal to its intracellular domain to modify the cytoskeleton and facilitate cell shape changes underlying morphogenesis.The attachment of cells to extracellular substrates-for example, by integrins (1)-plays an important role in determining cell shape and the intracellular organization of the cytoskeleton. Likewise, detachment of cells from substrates also leads to profound changes in cell shape and cytoskeletal organization. In particular, cell surface-associated proteases have been shown to mediate cell shape changes by local degradation of extracellular matrices and by signaling the reorganization of the actin cytoskeleton (2, 3). Proteases are also implicated in morphogenesis of imaginal discs to form adult appendages in Drosophila (4-7). The formation of legs and wings from discs results in part from actin-and myosindependent cell shape changes in the disc epithelium elicited by the steroid hormone 20-hydroxyecdysone (20HE) (8). Later in development, specific disc cells undergo actinmediated cell shape changes to form bristles (9, 10). Stubblestubbloid (Sb-sbd) mutants cause failures in cell-shape changes required for both disc and bristle morphogenesis. Gain-of-function Sb mutations affect bristle morphogenesis in a dominant manner. Both Sb and allelic loss-of-function sbd mutations act recessively to affect disc morphogenesis, producing characteristically malformed legs and wings (11).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.We show here...

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The organization of septate junctions during morphogenesis of imaginal disks is described from freeze-fracture replicas and thin sections with a view to understanding junction modulation during rearrangements of cells in epithelia. The septate junctions of each epithelial cell of the disk are distributed in a number of discrete domains equal to the number of neighboring cells. Individual septa traverse domains of contact between pairs of adjacent cells, turn downwards at the lateral boundary of the domain and run parallel to the intersection with a third cell. This arrangement leaves small channels at three-cell intersections that are occupied by specialized structures termed "tricellular plugs." Cell rearrangement involves a progressive change in the width of contact domains between adjacent cells, until old contacts are broken and new ones established. It is proposed that the septate junction adjusts to the changing width of domains by the compaction or extension of existing septa. This redistribution of septa theoretically allows a transepithelial barrier to be maintained during cell rearrangements. The applicability of this model to other epithelial tissues is discussed.The morphogenesis of an epithelium has previously been assumed to be limited to movements of entire epithelial sheets, with each cell within the epithelium retaining its immediate neighbors (1, 2). The presence of specialized connections between adjacent epithelial cells and the absence of morphological evidence of locomotion undoubtedly contributed to this view. However, rearrangements of cells (i.e., cell movements involving change of neighbors within a contiguous epithelial sheet) have recently been described during the evagination of imagined disks in Drosophila (3,4), neurulation in newts (5), gastrulation in Xenopus (6), regeneration in Hydra (7), and epiboly in teleosts (8). Thus, cell rearrangement appears to be a widespread phenomenon in epithelial morphogenesis.In most of the examples cited above, intercellular junctions persist during cell rearrangement (3,(6)(7)(8). Because junctions are sites of intercellular adhesion between pairs of adjacent cells, the exchange of neighbors requires some form ofjnnction modulation (9). Tight junctions of vertebrates and septate junctions of invertebrates present particularly formidable bartiers to cell rearrangement because they bridge or close off the intercellular space between a given cell and all of its neighbors, ensuring contiguity of the epithelial layer and providing a barrier to the extracellular movement of molecules across the epithelium (10-12). Thus, each cell appears to be fixed with respect to its neighbors. This paper focuses on the distribution of septa and the potentially dynamic organization of the septate junction during cell rearrangement in imagined disks. The detailed structure of the septate junction is well known. Rows of septa connect adjacent ceils and separate the apical from the basal intercellular space. The plasma membranes on both sides of a septum conta...

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