Étude du rôle d'un gène jouant un rôle potentiel dans la voie de signalisation de Hedgehog chez la drosophile

Résumé du document

Nous allons nous concentrer ici sur la voie de signalisation de Hedgehog (Hh) chez la Drosophile. Hh est connu pour être l'un des gènes de polarité des segments exprimés durant la phase tardive du développement embryonnaire de Drosophila melanogaster. Les gènes de polarité des segments sont ceux codant les protéines qui vont mettre en place la polarité anterio-postérieure des segments, unités de développement des embryons de Drosophile, une fois que la cellularisation s'est produite. Le Hh est une protéine sécrétée qui, une fois liée à son récepteur, va activer une cascade de signaux de transduction.

Extraits

[...] Bijlsma et.al. (2004), BioEssays pp. 387-394. In vivo evidence that Patched and Smoothened constitute dinstinct binding and transducing components of a Hedgehog receptor complex, Y. Chen and G. Struhl (1998), Development 125, pp. 4943-4948. Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface, R. Nusse (2003), Development 130, pp Websites: http://www.bio.davidson.edu/courses/genomics/method/reporters.html, reporter proteins, date accessed 7/03/06. [...]

[...] If our gene really is encoding the protein activating the kinase, we should observe a normal phenotype in the smo- mutants. On another hand, if we suspect the gene we found to encode one of the kinases that phosphorylate Fu or Cos2, the simpliest way would be to knock it out, once again using the RNA interference technique. Because the pathway would be disrupted, knocked out flies should not be able to express the Hh target genes. Hh can be found to be called “versatile”. [...]

[...] http://www.stanford.edu/group/hopes/treatmts/pbuildup/h2.html, interference, date accessed 10/03/06. [...]

[...] The second one is regarding the way that Smo uses to signal downstream to the microtubule bound complex and Ci. The possibility of a physical interaction between Smo and Ptc leading to a conformational change when Hh ligand is binding, thus relieving the inhibition of Ptc on Smo, has been raised but evicted, as it has been found that no colocalization is needed and that Ptc still inhibits Smo when present in a lower amount at cell surface thus eliminating any kind of stochiometric relation between the two proteins. [...]

[...] Hh is known to be one of the segment polarity genes expressed during the late phase of embryo development in Drosophila melanogaster. The segment polarity genes, as the name could say by itself, are the genes encoding proteins that will set up the anterio-posterior polarity of the segments, developmental units of Drosophila embryos, once cellularisation has occurred. Hedgehog is a secreted protein that will activate a signal transduction cascade once bound to its receptor. We will first see what is nowadays known about the hedgehog signalling pathway, including what happens before to the Hedgehog protein and some target genes, though both aspects are not properly regarding the signalling pathway, but are important to understand such a blur event in the patterning of future adult fly. [...]