ABSTRACT
Background: The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure. We performed RNAsequencing on the forming chick trigeminal ganglion and identified Elongator acetyltransferase complex subunit 1 ( Elp1 ) for further study. Mutations in ELP1 cause familial dysautonomia (FD), a fatal disorder characterized by the presence of smaller trigeminal nerves and sensory deficits. While Elp1 has established roles in neurogenesis, its functions in placode cells during trigeminal gangliogenesis have not been investigated. Results: To this end, we used morpholinos to deplete Elp1 from chick trigeminal placode cells. Elp1 knockdown decreased trigeminal ganglion size and led to aberrant innervation of the eye by placode-derived neurons. Trigeminal nerve branches exhibited fewer axons, and abnormal interactions between placode-derived neurons and neural crest cells were observed. Conclusions: These findings reveal a new role for Elp1 in chick placode-derived neurons during trigeminal ganglion development. These results have potential high significance to provide new insights into trigeminal ganglion development and the etiology of FD. Bullet points: Elp1 is expressed in undifferentiated neural crest cells and placode-derived neurons contributing to the trigeminal ganglion.Elp1 knockdown in trigeminal placode cells reduces trigeminal ganglion size.Elp1 depletion from trigeminal placode cells leads to aberrant target tissue innervation and disrupts proper neural crest-placodal neuron interactions in the trigeminal ganglion. Grant sponsor and number: NIH R01DE024217 and NIH R03HD108480.
ABSTRACT
The trigeminal ganglion contains the cell bodies of sensory neurons comprising cranial nerve V, which relays information related to pain, touch, and temperature from the face and head to the brain. Like other cranial ganglia, the trigeminal ganglion is composed of neuronal derivatives of two critical embryonic cell types, neural crest and placode cells. Neurogenesis within the cranial ganglia is promoted by Neurogenin 2 (Neurog2), which is expressed in trigeminal placode cells and their neuronal derivatives, and transcriptionally activates neuronal differentiation genes such as Neuronal Differentiation 1 (NeuroD1). Little is known, however, about the role of Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. To address this, we depleted Neurog2 and NeuroD1 from trigeminal placode cells with morpholinos and demonstrated that Neurog2 and NeuroD1 influence trigeminal ganglion development. While knockdown of both Neurog2 and NeuroD1 affected innervation of the eye, Neurog2 and NeuroD1 had opposite effects on ophthalmic nerve branch organization. Taken together, our results highlight, for the first time, functional roles for Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. These studies shed new light on the molecular mechanisms underlying trigeminal ganglion formation and may also provide insight into general cranial gangliogenesis and diseases of the peripheral nervous system.