Drosophila Lyra mutations are gain-of-function mutations of senseless.

The Lyra mutation was first described by Jerry Coyne in 1935. Lyra causes recessive pupal lethality and adult heterozygous Lyra mutants exhibit a dominant loss of the anterior and posterior wing margins. Unlike many mutations that cause loss of wing tissue (e.g., scalloped, Beadex, cut, and apterous-Xasta), Lyra wing discs do not exhibit increased necrotic or apoptotic cell death, nor do they show altered BrdU incorporation. However, during wing disc eversion, loss of the anterior and posterior wing margins is apparent. We have previously shown that senseless, a gene that is necessary and sufficient for peripheral nervous system (PNS) development, is allelic to Lyra. Here we show by several genetic criteria that Lyra alleles are neomorphic alleles of senseless that cause ectopic expression of SENSELESS in the wing pouch. Similarly, overexpression of SENSELESS in the wing disc causes loss of wing margin tissue, thereby mimicking the Lyra phenotype. Lyra mutants display aberrant expression of DELTA, VESTIGIAL, WINGLESS, and CUT. As in Lyra mutants, overexpression of SENSELESS in some areas of the wing pouch also leads to loss of WINGLESS and CUT. In summary, our data indicate that overexpression of SENSELESS causes a severe reduction in NOTCH signaling that in turn may lead to decreased transcription of several key genes required for wing development, leading to a failure in cell proliferation and loss of wing margin tissue.

Epithelial polarity and cell separation in the neoplastic l(1)dlg-1 mutant of Drosophila.

Lethal (1) discs-large-1 [l(1)dlg-1] is a non-epithelial overgrowth or neoplastic mutant of Drosophila, which results in tumor-like imaginal discs and enlarged larvae that never pupariate. In an ultrastructural analysis we found that the wing discs develop convoluted monolayers of epithelial cells characterized by well-defined apical-basal polarity and that these layered cells secrete large amounts of basement membrane material. Immuno-EM indicates that Drosophila laminin and collagen are components of this matrix. Late in development clusters or 'rosettes' of separated cells lacking cell-cell junctions and apical-basal polarity form. In in vitro culture experiments l(1)dlg-1 wing discs did not respond to a pulse of exogenous ecdysone by secreting cuticle or losing basement membrane as normal discs do. Our observations are consistent with the hypothesis that cell-cell interaction and communication is required for termination of disc cell proliferation, which must occur prior to a cellular response to ecdysone.

Ultrastructure of cell death in gamma- or X-irradiated imaginal wing discs of Drosophila.

When Drosophila larvae were irradiated with 1300-1500 R of gamma rays both apoptotic and necrotic cell death were observed in imaginal wing discs. The ultrastructure of cell death by apoptosis was characterized by fragmentation of dead cells into highly condensed, membrane-bound particles. The ultrastructure of cell death by necrosis was characterized by cell lysis and organelle degeneration. Marked contrast was also seen in the distribution of the two types of cell death: apoptosis was universal in irradiated discs and affected widely distributed single cells, or small groups of cells, whereas necrosis formed lesions by afflicting large numbers of contiguous cells. It was noted that even where there were large lesions in the epithelial cell layer, which is the primary component of imaginal discs, the basement membrane associated with this epithelium always remained intact. Lesions could be identified in freshly extirpated discs by staining with trypan blue and were found in 50-70% of irradiated discs (depending on the larval age at the time of irradiation). Lesions were seen in all regions of the wing disc and varied greatly in size. In spite of extensive necrotic cell death wing discs developed into normal adult wings. Regenerative growth in this case would appear to require significant reorganization of cells. Implications of this for the appropriate interpretation of clonal analysis are discussed.

Changes in mesenchymal cell-shape, matrix collagen and tenascin accompany bud formation in the early chick lung.

In the chick, lung branches arise as buds from the center of the pre-existing mesobronchial tube. Budding is known to be controlled by the mesenchyme. We have investigated mesenchymal properties in budding vs non-budding regions of the early chick lung, including sources of mesenchyme, cell shapes and densities, morphology and composition of the basement membrane, and distribution of the ECM components collagen, fibronectin and tenascin. We found that at points of outgrowth--the buds and the distal tip of the mesobronchus-mesenchymal cells adjacent to the lung epithelium are flattened, and the basement membrane is markedly thinned. In these basement membranes collagen is largely absent and tenascin redistributed into amorphous clumps. Of these characteristics only the cell-shape change, which results in the flattened mesenchymal cells at the bud tips, is correlated with initiation of the bud. We suggest that the cell-shape change leads to localized loss of collagen, which promotes emergence of buds, and that tenascin, which is found in the mesenchyme only in the budding region, promotes outgrowth and elongation of the bud.

Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila.

The senseless (sens) gene is required for proper development of most cell types of the embryonic and adult peripheral nervous system (PNS) of Drosophila. Sens is a nuclear protein with four Zn fingers that is expressed and required in the sensory organ precursors (SOP) for proper proneural gene expression. Ectopic expression of Sens in many ectodermal cells causes induction of PNS external sensory organ formation and is able to recreate an ectopic proneural field. Hence, sens is both necessary and sufficient for PNS development. Our data indicate that proneural genes activate sens expression. Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs.