N-cadherin facilitates trigeminal sensory neuron outgrowth and target tissue innervation

During the development of the sensory nervous system, various cell types converge to form different tissues. The trigeminal ganglion houses the cell bodies for the trigeminal nerve and exemplifies these intercellular interactions, as it is formed from the condensation of two diverse precursor cell populations, neural crest cells and placode cells. The dual origin of the trigeminal ganglion has been understood for decades, but the molecules that orchestrate this process remain relatively unknown. Assembling the trigeminal ganglion is mediated by cell adhesion molecules including the protein neural cadherin (N-cadherin), expressed first in placode-derived neurons and later in all trigeminal sensory neurons. Prior studies have shown that N-cadherin knockdown in chick trigeminal placode cells leads to early defects in trigeminal ganglion assembly by impacting the ability of placode-derived neurons to properly condense with undifferentiated neural crest cells. Later functions for N-cadherin in chick trigeminal gangliogenesis, however, are unknown. Using morpholino-mediated knockdown of N-cadherin in chick trigeminal placode cells, we examined trigeminal ganglion development at later developmental stages, when neural crest cells are differentiating into neurons. Through these experiments, we uncovered a sustained negative impact on the trigeminal ganglion, leading to decreases in ganglion size, nerve outgrowth, and branching to target tissues in vivo. Further, blocking the adhesive function of N-cadherin reveals its importance in the outgrowth ability for some, but not all, trigeminal neurons in vitro. These deficits reflect potential cell and non-cell autonomous effects on placodal and neural crest-derived neurons, respectively, and point to the importance of N-cadherin-mediated adhesion among trigeminal sensory neurons. Our findings reveal continued adhesion-dependent functions for N-cadherin in the trigeminal ganglion, which will aid in the understanding of its tissue-specific roles.