Exquisite regulation of Hox protein activity is fundamental to the regionalization of the early embryo across diverse taxa. Highlighting the critical importance of these transcription factors, an astonishing number of different mechanisms have evolved to tightly coordinate their activity both in time and in space. The recent identification of numerous microRNAs that are not only embedded within Hox clusters but also target numerous Hox genes suggests an important role for these regulatory molecules in shaping Hox protein output. Here, we discuss the positioning of these miRNAs within clusters over evolutionary time, the unexpected complexity in miRNA processing and target interactions, and the current understanding of Hox-embedded miRNA function during development.
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