Estudio de los mecanismos implicados en la morfogénesis de las articulaciones distales de la pata de Drosophila

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Centro de Biología Molecular "Severo Ochoa". Fecha de lectura: 25-05-2007Morphogens are secreted signaling molecules which control the patterning of many tissues. In the Drosophila wing disc, the TGFβ homolog Decapentaplegic (Dpp) forms a smooth gradient of activity and specifies cell fates by inducing or maintaining the expression of different target genes at distinct concentration thresholds. In this way, neighboring cells of the developmental field have similar amounts of the Dpp product, and if a sharp discontinuity in Dpp activity is generated between these cells, thus altering the Dpp gradient, JNKdependent apoptosis is triggered to restore graded positional information. To date, it has been assumed that this apoptotic process is only activated when normal signaling is distorted. We have found, however, that a similar process occurs during normal development. In this work we show that abrupt changes in Dpp activity take place during normal segmentation of the distal legs of Drosophila. In particular, these boundaries in Dpp signaling are located at the presumptive joint regions and, independently of the absolute level of Dpp activity, induce JNK/reaper dependent apoptosis required for the morphogenesis of the distal leg joints. Moreover, we show that this reaper expression is also under the regulation of the Notch pathway, which is a key element in leg joint morphogenesis and seems to be required for the formation of Dpp activity boundaries in the presumptive joints. In this work we have also found a novel Notch target gene in the legs, the gene zing finger homeodomain-2 (zfh-2), which, like JNK/reaper dependent apoptosis, is only required for the formation of distal leg joints. Interestingly, our results suggest that zfh-2 could be acting downstream of Notch to regulate the formation of sharp Dpp activity borders in the distal leg