Cell elimination strategies upon identity switch via modulation of apterous in Drosophila wing disc

Abstract

The ability to establish spatial organization is an essential feature of any developing tissue and is achieved through well-defined rules of cell-cell communication. Maintenance of this organization requires elimination of cells with inappropriate positional identity, a poorly understood phenomenon. Here we studied mechanisms regulating cell elimination in the context of a growing tissue, the Drosophila wing disc and its dorsal determinant Apterous. Systematic analysis of apterous mutant clones along with their twin spots shows that they are eliminated from the dorsal compartment via three different mechanisms: relocation to the ventral compartment, basal extrusion, and death, depending on the position of the clone in the wing disc. We find that basal extrusion is the main elimination mechanism in the hinge, whereas apoptosis dominates in the pouch and in the notum. In the absence of apoptosis, extrusion takes over to ensure clearance in all regions. Notably, clones in the hinge grow larger than those in the pouch, emphasizing spatial differences. Mechanistically, we find that limiting cell division within the clones does not prevent their extrusion. Indeed, even clones of one or two cells can be extruded basally, demonstrating that the clone size is not the main determinant of the elimination mechanism to be used. Overall, we revealed three elimination mechanisms and their spatial biases for preserving pattern in a growing organ.

Elimination Of Aberrantly Specified Cell Clones Is Independent Of Interfacial Myosin II Accumulation

“…Fortunately, such cells can be detected and effectively removed from the tissue [4][5][6][7]. However, the mechanism by which this happens is largely unknown.…”

“…Crucially, if clones of cells mutant for a selector gene arise in a compartment where this gene is expressed, the clones are either relocated to the opposite compartment or eliminated from the tissue completely [7,[31][32][33][34]. Cell sorting (relocation) and elimination were also reported for clones that ectopically express a range of other fate specifying transcription factors (including cubitus interruptus, vestigial, homothorax, Iroquois Complex, spalt and optomotor-blind) [4,[35][36][37][38].…”

“…Thus, cells with inappropriate positional identity, which occasionally arise due to sporadic mutations or chromatin defects, are detrimental for the whole organism. Fortunately, such cells can be detected and effectively removed from the tissue [4–7]. However, the mechanism by which this happens is largely unknown.…”

“…Cells that lack Apterous activity are eliminated from the dorsal compartment of the wing disc, whereas cells that ectopically express Apterous are removed from the ventral part (Fig. 1A) [7, 34]. There are at least three mechanisms involved in the clearance: relocation to the identity-appropriate compartment, apoptosis, and basal extrusion [7].…”

“…1A) [7, 34]. There are at least three mechanisms involved in the clearance: relocation to the identity-appropriate compartment, apoptosis, and basal extrusion [7]. Interaction of ap -expressing and ap -non-expressing cells at the boundary of misspecified clones induces ectopic activation of Notch and Wingless signaling.…”