Cell elimination strategies upon identity switch via modulation ofapterousinDrosophilawing disc

Abstract

15The ability to establish spatial organization is an essential feature of any developing tissue and 16 is achieved through well-defined rules of cell-cell communication. Maintenance of this 17 organization requires elimination of cells with inappropriate positional identity, a poorly 18 understood phenomenon. Here we studied mechanisms regulating cell elimination in the 19 context of a growing tissue, the Drosophila wing disc and its dorsal determinant Apterous. 20 Systematic analysis of apterous mutant clones along with their twin spots shows that they are 21 eliminated from the dorsal compartment via three different mechanisms: sorting to the 22 ventral compartment, basal extrusion, and death, depending on the position of the clone in 23 the wing disc. We find that basal extrusion is the main elimination mechanism in the hinge, 24 whereas apoptosis dominates in the pouch and in the notum. In the absence of apoptosis, 25 extrusion takes over to ensure clearance in all regions. Notably, clones in the hinge grow larger 26 than those in the pouch, emphasizing spatial differences. Mechanistically, we find that limiting 27 cell division within the clones does not prevent their extrusion. Indeed, even clones of one or 28 two cells can be extruded basally, demonstrating that the clone size is not the main 29 determinant of the elimination mechanism to be used. Overall, we revealed three elimination 30 mechanisms and their spatial biases for preserving pattern in a growing organ. 31 33 34Multicellularity requires precise spatial organization of cells during development. 35 Aberrant cells that arise as a result of sporadic mutations or chromatin defects can challenge 36

Bilateral JNK activation is a hallmark of interface contractility and promotes elimination of aberrant cells

“…S1P,Q). Similarly, previous studies demonstrate pattern-specific clone smoothening or even cyst formation for mosaic discs carrying LOF mutations in vg [27], Iro-C [42], omb [43], ci [47], ap [48], en [49] or Polycomb complexes [33]. Combined, these data highlight that aberrant cells, as identified by relative mispositioning with respect to the fate of surrounding cells, induce interface contractility hallmarks.…”