Hox genes code for an important family of transcription factors, which organise structures during animal development. In mammals, they are grouped into four different genomic clusters and these genes are active in many different structures, at various times. For example, they are necessary to organise the vertebral column early on, but also the intestin and the uro-genital apparatus -for example- subsequently.
How is this possible? Which are the regulatory mechanisms that can control these genes faithfully, yet in different contexts and at different times? And how did these mechanisms evolve from our invertebrate ancestors? These are the main question that this grant application wants to answer, i.e. what is the precise nature of the regulatory choreography that determine when and where which Hox gene(s) is (are) either active or silent.
Besides the importance of this work as a paradigm for gene regulation, it also impacts the society in two different aspects. First, more and more genetic diseases turn out not to be due to problems in the genes themselves but instead in their regulatory sequences. This is the case with Hox genes and many syndromes affecting their regulations have been described lately. Secondly, the precise understanding of these complex regulatory circuits will shed light on the multiple effects that such diseases often elicit ('syndromes'). This is of course due to the intrication of their regulations and hence it is important to understand how this works and consequently, how this was built over evolution.
