13-P105 In vivo recombination of two BAC clones to recreate the transcriptional landscape of the Pax3:FoxO1 fusion gene in Alveolar Rhabdomyosarcoma

We have shown previously that Notch is involved in neuronal subtype specification in the epiphysis, a simple structure containing only two neural subtypes: projection neurons and photoreceptors. Our data suggest that two distinct signals are required for photoreceptor fate specification: one, involving Notch, for the inhibition of projection neuron traits and the other for the induction of the photoreceptor fate (Cau et al., 2008). A candidate approach has allowed us to identify the BMP (Bone Morphogenetic Proteins) signalling pathway as the photoreceptor-inducing signal. Indeed, reducing the activity of the BMP signalling pathway using either the transgenic line Tg(hs:dn-bmpr) or Tg(hs:nog3) results in a decrease of photoreceptor production while conversely, forced activation of the pathway using the transgenic line Tg(hs:bmp2b) promotes the photoreceptor identity at the expense of projection neurons. Altogether, these results demonstrate that BMP is both necessary and sufficient for the production of photoreceptors. Interestingly, our preliminary results suggest that the BMP and the Notch signalling pathways cooperate for the transcriptional regulation of target genes such as members of the homolog enhancer of split (her), a family of bHLH transcription factors. We are currently studying the molecular mechanism underlying the interactions between the Notch and the BMP signalling pathways.