Myo-Inositol Synthesis In Drosophila Melanogaster Effects Development

Myo ‐inositol is an essential metabolite that plays an important role in development, osmoregulation, and disease states such as diabetes, bipolar disorder and spinal chord defects. Inositol is synthesized from glucose‐6‐phosphate by myo ‐inositol‐1‐phosphate synthase ( MIPS ). More than 75% of genes involved in human diseases have orthologs in the model system Drosophila melanogaster . The MIPS gene of D. melanogaster encodes a protein 62.2 kDa (pI=6.17) and is 58.5% identical (72.3% similar) to the human MIPS protein. In silico experiments have revealed regulatory sequences responsive to inositol, osmotic and/or oxidative stress. MIPS RNA has been shown to be highly expressed in the fly head, hindgut, ovary and testis (FlyAtlas, 2007). Preliminary examination of a MIPS mutant D. melanogaster strain revealed reduced fecundity in crosses with homozygous mutant males. Further analysis suggested that reduced fecundity is due to defective sperm. Inositol metabolism was also examined by growing flies on defined media with sucrose or inositol as the energy source. Inositol‐grown flies demonstrated a reduction in eggs laid but progress normally through development. Proteomic analyses revealed many differences between crude lysates of flies grown on sucrose versus inositol.