Interplay between cell proliferation and recruitment controls the duration of growth and final size of the Drosophila wing

How organs robustly attain a final size despite perturbations in cell growth and proliferation rates is a fundamental question in developmental biology. Since organ growth is an exponential process driven mainly by cell proliferation, even small variations in cell proliferation rates, when integrated over a relatively long time, will lead to large differences in size, unless intrinsic control mechanisms compensate for these variations. Here we use a mathematical model to consider the hypothesis that in the developing wing of Drosophila, cell recruitment, a process in which undifferentiated neighboring cells are incorporated into the wing primordium, determines the time in which growth is arrested in this system. Under this assumption, our model shows that perturbations in proliferation rates of wing-committed cells are compensated by an inversely proportional duration of growth. This mechanism ensures that the final size of the wing is robust in a range of cell proliferation rates. Furthermore, we predict that growth control is lost when fluctuations in cell proliferation affects both wing-committed and recruitable cells. Our model suggests that cell recruitment may act as a temporal controller of growth to buffer fluctuations in cell proliferation rates, offering a solution to a long-standing problem in the field. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/444212v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@13b7947org.highwire.dtl.DTLVardef@1973142org.highwire.dtl.DTLVardef@122ec0dorg.highwire.dtl.DTLVardef@1b7513e_HPS_FORMAT_FIGEXP M_FIG C_FIG