ROLE OF ANNEXIN A6 IN SENSORY NEURONS DURING EARLY CHICK CRANIAL GANGLIA DEVELOPMENT

The cranial sensory ganglia are created from neural crest cells and placode cell-derived neurons. Defects in the migration and interaction of these cells can cause abnormalities in craniofacial development and the sensory nervous system. To this end, we are using the embryonic chick cranial ganglia to elucidate the signaling mechanisms underlying cellular interactions. The Annexin protein superfamily has an evolutionarily conserved role in the development of the sensory ganglia. Our lab previously identified a function for chick Annexin A6 in modulating early NCC migration, but a later role for Annexin A6 in cranial ganglia assembly has not been investigated. We hypothesize that Annexin A6 acts a core cytoskeletal scaffold in cranial ganglia neurons to facilitate cranial ganglia formation. In support of this, our results show that placode cell-derived neurons express Annexin A6 during cranial ganglia assembly, and that expression is maintained throughout cranial gangliogenesis. Annexin A6 is also observed in neurons within the dorsal root ganglia and ventral neural tube, suggesting that Annexin A6 may be a specific neuronal marker. To investigate the function of Annexin A6 within the placode cells of the assembling cranial ganglia, we used a gene perturbation approach. Annexin A6 depletion from developing placode cells does not affect placode cell-derived neurons’ position within the ganglionic anlage nor disturb the surrounding neural crest cell corridors. Annexin A6 knockdown in placode cells results in neurons that produce very few short and/or no axonal projections instead of the normal bipolar morphology observed in the presence of Annexin A6. Placode cell-derived neurons with reduced level of Annexin A6 still express mature neuronal markers, they do not possess two long processes, which are characteristic morphological features of mature neurons, and fail to innervate their designated targets due to the absence of this bipolar morphology. In keeping with these results, Annexin A6 overexpression causes some placode cell-derived neurons to form extra protrusions alongside these bipolar processes. These data demonstrate that the molecular program associated with neuronal maturation is distinct from that orchestrating changes in neuronal morphology, and, importantly, reveal Annexin A6 to be a key membrane scaffolding protein during neuron membrane biogenesis