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

PLoS Genet. 2019 Dec 26;15(12):e1008573. doi: 10.1371/journal.pgen.1008573. eCollection 2019 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • LIM-Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins / metabolism
  • Mutation
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Wings, Animal / growth & development*
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • LIM-Homeodomain Proteins
  • Transcription Factors
  • ap protein, Drosophila

Grants and funding

This work has been supported by the Swiss National Science Foundation professorship grants to F.H. (PP00P3_150682 and PP00P3_179075) and by the Ser Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government (80762-CU186). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.