Fat body secreted SPARC promotes Ilp2 release and systemic growth in Drosophila larvae

Abstract Background The growth of Drosophila larvae is strongly influenced by the available food. Depending on the quality and quantity of ingested nutrients, the larval fat body secretes systemic signals that control the growth of other organs. The identity of these signals is not fully understood yet. Results We describe a reporter-based in vivo screen that allowed the systematic gene knockdown in the signal-producing fat body and simultaneously measured the resulting growth effects in the signal-receiving larval peripheral tissues. This screen led to the identification of the matricellular protein SPARC/BM-40 (Secreted protein acidic and rich in cysteine/Basement-membrane protein 40) as a novel factor controlling the release of insulin from neurosecretory cells and thereby controlling systemic animal growth. Synthetic human SPARC can substitute for Drosophila SPARC, revealing a novel evolutionarily conserved signaling axis. Conclusions The evolutionarily conserved protein SPARC is identified as a novel incretin-like signal that can promote the endocrine release of insulin in vivo.