Abstract
How cell to cell interactions control local tissue growth to attain a species-specific pattern and organ size is a central question in developmental biology. The Drosophila Neural Cell Adhesion Molecule, Fasciclin 2 (Drosophila NCAM), is expressed during the development of neural and epithelial organs. Genetic mosaic analysis of Fasciclin 2 reveals two complementary and opposing functions during imaginal disc growth, a cell autonomous requirement to promote growth and an opposite non-cell autonomous function to restrain growth at high expression levels. This non-cell autonomous function is mediated by the Fasciclin 2 heterophilic-binding partners CG15630 and CG33543. We further show that EGFR physically interacts with Fasciclin 2 and mediates both the cell autonomous and the non-cell autonomous function. We also show that EGFR activity in turn promotes the cell autonomous expression of Fasciclin 2. We suggest that the autostimulatory loop between EGFR and Fasciclin 2 operates until reaching a threshold where the Fasciclin 2 non-cell autonomous function counteracts the growth-promoting activity of the homophilic interaction to terminate imaginal disc growth. In this scenario, cellular integration of Fasciclin 2 autonomous and non-cell autonomous signaling from neighbor cells may be a key regulator component to orchestrate the rate of intercalary cell proliferation and the final size of an organ.
Footnotes
↵3 Present address: Instituto de Investigaciones Biomedicas “Alberto Sols” CSIC-UAM, Universidad Autonoma de Madrid. Arturo Duperier 4, Madrid 28029. Spain.