The TRIM-NHL RNA-binding protein MEI-P26 modulates the size of Drosophila Type I neuroblast lineages.

Abstract

The Drosophila TRIM-NHL RNA-binding protein (RBP), MEI-P26, has previously been shown to suppress tumor formation in the germline. Here we show that, in the Drosophila larval central brain, cell-type specific expression of MEI-P26 plays a vital role in regulating neural development. MEI-P26 and another TRIM-NHL RBP, Brain tumor (BRAT), have distinct expression patterns in Type I neuroblast (NB) lineages: While both proteins are expressed in NBs, BRAT is expressed in ganglion mother cells (GMCs) but not neurons whereas MEI-P26 is expressed in neurons but not GMCs. Knockdown of MEI-P26 leads to re-expression of the stem cell marker Deadpan (DPN) and over-production of neurons. In contrast, ectopically expressed MEI-P26 reduces NB lineage size by repressing division of GMCs, resulting in reduced neuron production. We show that MEI-P26 positively regulates expression of Prospero (PROS), a transcription factor that is known to repress cell cycle related genes. Ectopic expression of PROS phenocopies ectopic expression of MEI-P26. In both cases, Cyclin B (CYCB) expression is downregulated. Importantly, knockdown of PROS in the context of ectopic MEI-P26 rescues the neural lineage. Based on these results, we conclude that MEI-P26 functions to prevent over-production of neurons by promoting production of PROS which, in turn, downregulates cell division.