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Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Cells no longer needed are quickly removed without compromising barrier function of the tissue. During metamorphosis, insects undergo developmentally programed tissue remodeling. However, the mechanisms that regulate this rapid tissue remodeling are not precisely understood. Here, we show that the temporal dynamics of endocytosis modulate physiological cell properties to potentiate larval epidermal cells for cell elimination. Endocytic activity gradually reduces as tissue remodeling progresses. This reduced endocytic activity accelerates cell elimination through the regulation of Myosin II subcellular reorganization, junctional E-cadherin levels, and caspase activation. Whereas the increased Myosin II dynamics accelerates cell elimination, E-cadherin rather plays a protective role against cell elimination. Reduced E-cadherin is involved in the amplification of caspase activation by forming a positive feedback loop with caspase. These findings reveal the role of endocytosis in preventing cell elimination and in the cell property switching initiated by the temporal dynamics of endocytic activity to achieve rapid cell elimination during tissue remodeling.

Tissue organization requires the interplay between biochemical signaling and cellular force generation. The formation of straight boundaries separating cells with different fates into compartments is important for growth and patterning during tissue development. In the developing Drosophila wing disc, maintenance of the straight anteroposterior (AP) compartment boundary involves a local increase in mechanical tension at cell bonds along the boundary. The biochemical signals that regulate mechanical tension along the AP boundary, however, remain unknown. Here, we show that a local difference in Hedgehog signal transduction activity between anterior and posterior cells is necessary and sufficient to increase mechanical tension along the AP boundary. This difference in Hedgehog signal transduction is also required to bias cell rearrangements during cell intercalations to keep the characteristic straight shape of the AP boundary. Moreover, severing cell bonds along the AP boundary does not reduce tension at neighboring bonds, implying that active mechanical tension is upregulated, cell bond by cell bond. Finally, differences in the expression of the homeodomain-containing protein Engrailed also contribute to the straight shape of the AP boundary, independently of Hedgehog signal transduction and without modulating cell bond tension. Our data reveal a novel link between local differences in Hedgehog signal transduction and a local increase in active mechanical tension of cell bonds that biases junctional rearrangements. The large-scale shape of the AP boundary thus emerges from biochemical signals inducing patterns of active tension on cell bonds.

Neural stem cells called neuroblasts (NBs) generate a variety of neuronal and glial cells in the central nervous system of the Drosophilaembryo. These NBs, few in number, are selected from a field of neuroepithelial(NE) cells. In the optic lobe of the third instar larva, all NE cells of the outer optic anlage (OOA) develop into either NBs that generate the medulla neurons or lamina neuron precursors of the adult visual system. The number of lamina and medulla neurons must be precisely regulated because photoreceptor neurons project their axons directly to corresponding lamina or medulla neurons. Here, we show that expression of the proneural protein Lethal of scute [L(1)sc] signals the transition of NE cells to NBs in the OOA. L(1)sc expression is transient, progressing in a synchronized and ordered `proneural wave' that sweeps toward more lateral NEs. l(1)sc expression is sufficient to induce NBs and is necessary for timely onset of NB differentiation. Thus, proneural wave precedes and induces transition of NE cells to NBs. Unpaired (Upd), the ligand for the JAK/STAT signaling pathway,is expressed in the most lateral NE cells. JAK/STAT signaling negatively regulates proneural wave progression and controls the number of NBs in the optic lobe. Our findings suggest that NBs might be balanced with the number of lamina neurons by JAK/STAT regulation of proneural wave progression, thereby providing the developmental basis for the formation of a precise topographic map in the visual center.

Photoreceptor cell axons (R axons) innervate optic ganglia in the Drosophila brain through the tubular optic stalk. This structure consists of surface glia (SG) and forms independently of R axon projection. In a screen for genes involved in optic stalk formation, we identified Fak56D encoding a Drosophila homolog of mammalian focal adhesion kinase (FAK). FAK is a main component of the focal adhesion signaling that regulates various cellular events, including cell migration and morphology. We show that Fak56D mutation causes severe disruption of the optic stalk structure. These phenotypes were completely rescued by Fak56D transgene expression in the SG cells but not in photoreceptor cells. Moreover, Fak56D genetically interacts with myospheroid, which encodes an integrin β subunit. In addition,we found that CdGAPr is also required for optic stalk formation and genetically interacts with Fak56D. CdGAPr encodes a GTPase-activating domain that is homologous to that of mammalian CdGAP, which functions in focal adhesion signaling. Hence the optic stalk is a simple monolayered structure that can serve as an ideal system for studying glial cell morphogenesis and the developmental role(s) of focal adhesion signaling.