Fasciclin 2 engages EGFR in an auto-stimulatory loop to promote imaginal disc cell proliferation in Drosophila

PLoS Genet. 2022 Jun 6;18(6):e1010224. doi: 10.1371/journal.pgen.1010224. eCollection 2022 Jun.

Abstract

How cell to cell interactions control local tissue growth to attain a species-specific organ size is a central question in developmental biology. The Drosophila Neural Cell Adhesion Molecule, Fasciclin 2, is expressed during the development of neural and epithelial organs. Fasciclin 2 is a homophilic-interaction protein that shows moderate levels of expression in the proliferating epithelia and high levels in the differentiating non-proliferative cells of imaginal discs. Genetic interactions and mosaic analyses reveal a cell autonomous requirement of Fasciclin 2 to promote cell proliferation in imaginal discs. This function is mediated by the EGFR, and indirectly involves the JNK and Hippo signaling pathways. We further show that Fasciclin 2 physically interacts with EGFR and that, in turn, EGFR activity promotes the cell autonomous expression of Fasciclin 2 during imaginal disc growth. We propose that this auto-stimulatory loop between EGFR and Fasciclin 2 is at the core of a cell to cell interaction mechanism that controls the amount of intercalary growth in imaginal discs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Drosophila / genetics
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • ErbB Receptors / genetics
  • Imaginal Discs*
  • Receptors, Invertebrate Peptide / genetics
  • Wings, Animal

Substances

  • Drosophila Proteins
  • Receptors, Invertebrate Peptide
  • Egfr protein, Drosophila
  • ErbB Receptors

Grants and funding

This work has been supported by grants from: Ministerio de Ciencia e Innovacion, BFU2016-76295-R (MCIN/AEI/10.13039/501100011033 and by “ERDF a way of making Europe”) to LGA; Generalitat Valenciana, Conselleria d’Educació, Investigació, Cultura i Esport, Prometeo 2021-027 to LGA; Ministerio de Ciencia y Tecnologia, SAF2004-06593 to LGA; Ministerio de Ciencia y Tecnologia, FP2001-2181 to EV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.