GENERAL DISCUSSION AND SUMMARY

The patterning of the anterior-posterior axis as done by the Hox genes forms one of the best characterized and most investigated regulatory systems within the field of developmental biology. Historically, it probably represents the first developmental problem to be seen with our modern understanding of gene biology; during the early 1980’s the Drosophila Antenapedia Hox complex was the first developmental genetic locus to be investigated with the, at that time, brand new toolbox of molecular biology. Despite their long history in biological research the Hox genes still receive the unrelenting attention from the scientific community. In Pubmed there are in total 4804 citations for ‘Hox*’ and the yearly number of papers published on the subject is still steadily on the increase (fig.1). Although all paradigms in the Hox field were set almost 2 decades ago, challenging discoveries are being made each year and novel developments from other fields are steadily incorporated in the framework of understanding on Hox functioning and dis-functioning. One of these breakthroughs from recent history is what is now sometimes referred to as the ‘non-coding RNA revolution’. Although it was already known at the time that small non coding RNAs could silence genes (Lee et al. 1993), it was not until the discovery of the mechanism of RNA interference that it was appreciated how widespread this regulatory mechanism is. The term microRNA itself was only introduced in 2001 (Ruvkun 2001). The impact of the discoveries made in 2001 and 2002 was deemed so great that Science magazine awarded it the title of ‘Breakthrough of the year 2002’ (Couzin 2002). Subsequently it turned out that genomes contain hundreds of non coding RNA genes, many of which are microRNAs but novel classes have been discovered more recently (e.g. Girard et al. 2006). From whole library sequencing projects, aimed at identifying all the microRNAs present in the genome, it appeared that two microRNA families are present within the Hox clusters, namely miR-10 and miR-196 which were both identified in 2003.