Cell-autonomous and non-autonomous growth-defective mutants of Drosophila melanogaster

During animal development, growth of the various tissues and organs that ma ke up the body must be coordinated, Despite recent progress in understandin g growth control within the cell unit, the mechanisms that coordinate growt h at the organismal level are still poorly understood. To study this proble m, we performed a genetic screen for larval growth-defective mutants in Dro sophila melanogaster, Characterization of these mutants revealed distinct t ypes of larval growth defects. An allelic series for the translation initia tion factor, Eif4A, showed different growth rates and suggests that Eif4A c ould be used as a dose-dependent growth regulator. Two mutants that fail to exit cellular quiescence at larval hatching (milou and eif4(1006)) have a DNA replication block that can be bypassed by overexpression of the E2F tra nscription factor. A mutation (bonsai) in a homolog of the prokaryotic ribo somal protein, RPS15, causes a growth defect that is non-cell-autonomous. O ur results emphasize the importance of translational regulation for the exi t from quiescence. They suggest that the level of protein synthesis require d for cell cycle progression varies according to tissue type, The isolation of non-cell-autonomous larval growth-defective mutants suggests that speci alized organs coordinate growth throughout the animal and provides new tool s for studies of organismal growth regulation.