The role of the transcription factor ZIC2 in neural crest development

Abstract

Neural Crest cells (NCCs) are pluripotent cells that originate in the dorsal neuroephithelium of the dorsal neural tube and travel all over the embryo to contribute to the formation of many organs. The zinc finger transcription factor Zic2 (Zinc Finger of the Cerebellum protein 2) is known to participate in several steps of neural development including neurulation and neural crest formation. However, its precise role in these processes has not been yet clearly stated. Here, we show that Zic2 is expressed in premigratory but not in migrating NCCs. Then, functional experiments in vivo demonstrate that Zic2 expression is crucial for the formation of the NNCs but does not regulate cell death or cell fate. In an unbiased gene-wide screen performed in the chick neural tube, we identified the secreted protein Draxin/Neucrin as a possible Zic2 effector. We then confirm that spatiotemporal expression of Zic2 and Draxin in the dorsal tube are very similar and, functional experiments in chick demonstrate that Zic2 regulates Draxin/Neucrin expression during NCC formation. Finally, loss of function and gain of function studies confirm that Draxin/Neucrin partially recapitulates Zic2 functions during NCC migration. All these experiments together demonstrate that Zic2 plays a critical role during the progression of NCCs to get out of the neural tube and reveal that Zic2 induces Draxin/Neucrin expression during this process.