DLMO a proneural activator in Drosophila is regulated by conserved microRNAs

The pattern of the external sensory organs depends on the activity of the bHLH transcriptional activators Achaete/Scute that provide the cell with a neural fate. The proper proneural activation in the dorsocentral region requires the formation of a complex where the Ldb protein Chip acts as a bridge between the GATA factor Pannier and the proneural bHLHs heterodimers. We proved that dLMO a LIM-Only protein acts within the DC complex as a proneural activator. The dLMO gain of function mutants have deletions of the dLMO 3’UTR. This region contains sites for conserved microRNAs. In fact, mir-9 regulates dLMO level through its 3’UTR, to assure the proper wing development. DLMO is the homolog of LMO2, a human hematopoetic oncogene found in similar complexes to the fly DC complex and linked to acute leukemia. We found that LMO2 level is regulated by the same ancient miRNAs in vitro. We expect that mir-9 could act as a tumor suppressor gene to regulate aberrant expression of LMO2 in leukemia.