Elucidating the Role of N‐cadherin during Trigeminal Gangliogenesis

Abstract

Cadherin‐based adhesion is critical to the formation of multicellular tissues, including the cranial sensory ganglia of the peripheral nervous system. Initial assembly of the cranial trigeminal ganglion, which houses the cell bodies for the trigeminal nerve, relies on the coalescence of N‐cadherin (N‐cad)‐expressing placode cell‐derived neurons and Cadherin‐7‐expressing neural crest cells. The trigeminal ganglion has a role that is primarily sensory, transmitting information on pain, touch, and temperature from different facial regions back to the central nervous system. Proper survival and differentiation of trigeminal neurons relies, in part, upon binding of neurotrophic and other growth factors secreted from target tissues to their cognate receptors found on peripheral axons. These complexes are then trafficked to neuronal cell bodies, resulting in the activation of downstream signaling pathways. Prior studies have shown that N‐cad internalization and trafficking are required for proper neuronal outgrowth. Moreover, N‐cad knockdown in chick trigeminal placode cells leads to early defects in trigeminal ganglion assembly by increasing placodal neuron dispersal. Later functions for N‐cad in chick trigeminal gangliogenesis, however, remain obscure. We hypothesize that N‐cad controls trigeminal ganglion development through the regulation of multiple signaling pathways. To address this, we performed morpholino‐mediated knockdown of N‐cad in chick trigeminal placode cells followed by immunohistochemistry and biochemistry to evaluate trigeminal gangliogenesis. Our preliminary data show that N‐cad depletion has a sustained negative impact on the trigeminal ganglion through cell and non‐cell autonomous effects, resulting in decreased ganglion size, aberrant nerve outgrowth and branching, and reduced levels of Cadherin‐7, neurotrophins and their receptors, and Smad family members. Future studies will aim to elucidate the mechanisms by which N‐cad controls trigeminal ganglion development via these molecules and pathways, including experiments designed to examine protein trafficking in trigeminal neurons. Taken together, our findings reveal potential adhesion‐dependent and ‐independent functions for N‐cad in the trigeminal ganglion, which will aid in the understanding of its tissue‐specific roles. This knowledge will shed light on the etiology of disorders characterized by abnormal neural crest cell and placode cell development and those affecting the peripheral nervous system.