CONICET | Buscador de Institutos y Recursos Humanos

Understanding the mechanisms by which multicellular organisms control the growth of cells, organs and the whole body is a central question in developmental biology. Studies in this field suggest that genetic mechanisms interlace with environmental clues to establish the final size of the organism. In this work, we describe the function of a novel gene that we have named zonda as a negative regulator of growth. eyeless-flippase-induced zonda mutant clones generate larger heads when compared to controls. Conversely, overexpression of zonda in the head tissue leads to a pinhead phenotype, and mosaic overexpression of zonda in larval fat body cells provokes an autonomous reduction in cell size. Strikingly, Zonda subcellular localization is sensitive to the nutritional status of the larvae. In well-fed individuals Zonda presents a vesiculo-reticulated subcelullar distribution, with out any clear colocalization with well- described organellar markers. When third instar larvae are fasted for 4 hours, Zonda distribution changes dramatically to discrete foci. Zonda-containing foci partially co-localize with lysotracker and Lamp1 positive vesicles, and strongly co-localize with ATG-8, indicating that under these conditions Zonda is part of autophagy-induced structures. This remarkable co-localization led us to investagate a potential role for Zonda as an autophagy gene. Indeed, we found that Zonda mutant clones in the fat body of starved third instar larvae fail to incorporate lysotracker, characteristic of starvation-induced autophagy. Even more, over-expression of Zonda is sufficient to induce autophagy, as assessed by the nucleation of ATG8 in autophagosomes. Altogether, our results reveal that Zonda is a novel autophagy gene likely to play a role at early steps of the autophagy cascade and with the capability to impact cell size.