Placode-derived orphan chemokine CXCL14 is critical for proper chick trigeminal ganglion formation.

The trigeminal ganglion, the largest of cranial sensory ganglia, has a dual origin from neural crest and ectodermal placode cells, which interact extensively during ganglion formation. In the developing chick embryo, we find that the orphan chemokine Cxcl14 is expressed in placode-derived cells at a time corresponding to when placode and neural crest cells, expressing the chemokine receptor Cxcr4, begin to condense into the trigeminal ganglion. In contrast, Cxcl12, the proposed canonical receptor for Cxcr4, is expressed in the frontonasal process and branchial arches, regions distant from the forming ganglion primordium. Importantly, CRISPR-Cas9 mediated knockout of Cxcl14 disrupted trigeminal ganglion formation, resulting in loss of the maxillomandibular lobe and reduction in the ophthalmic lobe as well as defective axonal projections. Taken together, these data reveal a new in vivo role for Cxcl14 during development and suggest a ligand-receptor interaction between CXCR4 and CXCL14, rather than CXCL12, during trigeminal ganglion development.