APC/CFzr/Cdh1 dependent regulation of cell adhesion controls glial migration in the Drosophila PNS

Marion Silies (1) , Christian C Klambt (1)

1 Institut für Neurobiologie

Neuron-glia interaction is a key feature during nervous system assembly. During development, glial cells often follow extending axons, implying a precise coordination between axonal outgrowth and glial migration. Here we assign a novel function to the anaphase-promoting-complex/cyclosome (APC/C) co-activator Fizzy-related/Cdh1 (Fzr/Cdh1) in non-autonomously controlling peripheral glial migration in postmitotic Drosophila neurons. APCFzr/Cdh1 is a well-described cell-cycle regulator that targets proteins required for G1 arrest for ubiquitination and subsequent degradation. We show that Fzr/Cdh1 function is mediated via the Ig-superfamily cell adhesion molecule Fasciclin2 (Fas2). In motor neurons Fzr/Cdh1 is critical for the establishment of a graded axonal distribution of Fas2. Axonal Fas2 protein interacts homophilically with a glial Fas2 isoform. Glial migration is initiated along axonal segments that present low Fas2 levels but stalls in axonal domains decorated with high levels of Fas2. This presents a simple mechanism how a subcellular gradient of adhesiveness coordinates glial migration with axonal growth.

Mots clés: Development; Glia

Marion Silies, Christian C Klambt. APC/CFzr/Cdh1 dependent regulation of cell adhesion controls glial migration in the Drosophila PNS. Nature Neuroscience, 2010, ⟨10.1038/nn.2656⟩. ⟨hal-00582636⟩