Jean-Maurice Dura Institut de Génétique Humaine jmdura@igh.cnrs.fr Guigage axonal dans le système nerveux ventral chez Drosophila: rôles du récepteur DRL et de son ligand WNT5 Callahan et al., Nature 1995 Bonkowsky et al., Nature 1999 Yoshikawa et al., Nature 2003

Strong similarities between Drosophila and human More than 50% of the 15.000 Drosophila genes have a strong similarity with a human gene. Amongst 289 human genes involved in a severe pathology, 177 have a clear homologue in Drosophila. Numerous molecular pathway are very well conserved (signal transduction; neurotransmitters; etc......).

Crible “enhancer trap” avec P[etau-lacZ] qui permet de bien visualiser les trajets axonaux - crible de 2400 nouvelles insertions au hasard.

drlP[etau-lacZ]/+ anti-gal +/+ anti-HRP drlP[etau-lacZ]/+ anti-gal 200 interneurons / hemisegment 20 interneurons / hemisegment

drlP : insertion - allèle perte de fonction - lacZ exprimé comme drl+ drlPexc : excision précise - allèle sauvage drlR : délétion - allèle null

drlP/+ drlP/+ [+] [+] drlP/drlP drlP/drlR [-] [-] defasciculation 10% cross in PC

drlP/drlPexc drlR/drlR [+] [-] anti-Fas2 anti-DRL @ 10h anti-DRL @ 11.5h

The DRL protein

30% cross in PC

drlP : insertion - allèle perte de fonction - lacZ exprimé comme drl+ drlPexc : excision précise - allèle sauvage drlR : délétion - allèle null drlRed2 : allèle null - lacZ exprimé comme drl+

in yeast GAL4 881 aa: regulator of transcription of genes induced by galactose (GAL10 and GAL1) by directly binding to 4 related 17 bp sites defining an Upstream Activating Sequences (UAS) in Drosophila (transgenesis via P transposable element) (no deleterious effect)

eagle-GAL4 + UAS-tau-lacZ +UAS-drl +UAS-drlE: cross in AC + PC cross only in AC cross in AC + PC

drl instructs crossing axons to choose AC: - attractive to AC? - repulsive to PC?

ap-GAL4/UAS-tau-lacZ ap-GAL4/UAS-tau-lacZ; 2xUAS-drl drl recognizes a repulsive cue in the PC

ap-GAL4/UAS-tau-lacZ + UAS-drl : no crossing - no effect + UAS-comm : crossing in AC +PC + UAS-comm + UAS-drl : crossing only in AC + UAS-comm + UAS-drlE : crossing in AC +PC