ZONDA: A NOVEL DROSOPHILA GENE INVOLVED IN GROWTH CONTROL

MARIANA MELANI; NURIA M. ROMERO; LUIS R. CASSINOTTI; MARIA J. ACEVEDO; PABLO WAPPNER

Congreso; VI International Meeting of the Latin American Society for Developmental Biology; 2012

Latin American Society for Developmental Biology

<!-- /* Font Definitions */ @font-face {font-family:Arial; panose-1:2 11 6 4 2 2 2 2 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Cambria; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi; mso-ansi-language:ES-TRAD;} @page Section1 {size:595.0pt 842.0pt; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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 regard, a reduction in oxygen concentration has a profound impact in organism size as has been largely described for the fruit fly Drosophila melanogaster. In an RNAi-based genome-wide screen in S2 cells we identified a novel Drosophila gene, which we have named zonda, as a regulator of the transcriptional response to hypoxia. Zonda is homologous to mammalian FKBP38, which was recently linked to the TOR pathway. The TOR signaling pathway is central in the regulation of growth in response to the nutritional status. Preliminary results from our laboratory suggest that zonda is a negative regulator of growth. Mosaic overexpression of zonda in Drosophila larval fat body cells leads to a dramatic reduction in cell size. Moreover, overexpression of zonda in the head tissue using the eyeless-Gal 4 driver leads to a pinhead phenotype. On the contrary, eyeless-flippase-induced zonda mutant clones generate larger heads when compared to controls. Zonda subcellular localization seems to be sensitive to the nutritional status. In well-fed larvae Zonda localization is homogeneous throughout the cytoplasm of fat body cells. However, Zonda localization gets punctate when third instar larvae are fasted for 4 hours. Zonda punctae partially localize with acidic lysotracker-sensitive vesicles and fully localize with autophagy-related vesicles labeled with ATG-8. We are currently performing genetic interaction and epistatic studies to determine weather zonda regulates cell size through the activation of the autophagy cascade or weather it has a more direct effect on the TOR signaling pathway.