Zonda: A novel gene involved in autophagy and growth control. Mariana Melani¹, Maria Julieta Acevedo¹, Joel Perez Perri¹, Nuria Magdalena Romero², Pablo Wappner¹. 1) Fundacion Instituto Leloir, Buenos Aires, Buenos Aires, Argentina; 2) Institute of Developmental Biology and Cancer, Nice, France.

   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 of 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, without any clear colocalization with well-described organellar markers. When third instar larvae are starved for 4 hours, Zonda distribution changes dramatically to discrete foci. Zonda-containing foci partially colocalize with lysotracker and Lamp1 positive vesicles, and strongly colocalize with ATG-8, indicating that under these conditions Zonda is part of autophagy-induced structures. This remarkable colocalization led us to investigate a potential role of Zonda in autophagy. 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. Moreover, overexpression 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, thereby modulating growth control.