Hox miRNA regulation within the Drosophila Bithorax complex: Patterning behavior

The study of Drosophila Hox genes, located in the Antennapedia complex (ANT-C) and Bithorax complex (BX-C), has provided fundamental insights into mechanisms of how the segments of the animal body plan are specified. Notably, even though the analysis of the BX-C formally began over a century ago, surprises continue to emerge regarding its regulation and function. Even simply the gene content of the BX-C has been regularly revised in past years, especially with regard to non-coding RNAs (ncRNAs), including microRNAs. In this perspective, we review the history of studies of non-coding transcription in the BX-C, and highlight recent studies of its miRNAs that provide new insights into their tissue-specific roles in Hox gene regulation. In particular, we have demonstrated unexpected importance of endogenous BX-C miRNAs to restrict the spatial accumulation of Hox proteins and their TALE cofactors in the ventral nerve cord, and link this to aberrant neural differentiation and reproductive behavior. These findings open new directions on studying Hox miRNA function, and we speculate that further understanding of their roles in insect models may provide new leads for studying the enigmatic biological functions of analogous miRNAs located in vertebrate Hox clusters.