Elp1 function in placode-derived neurons is critical for proper trigeminal ganglion development

Abstract

BackgroundThe 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. ResultsTo 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. ConclusionsThese 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 pointsO_LIElp1 is expressed in undifferentiated neural crest cells and placode-derived neurons contributing to the trigeminal ganglion. C_LIO_LIElp1 knockdown in trigeminal placode cells reduces trigeminal ganglion size. C_LIO_LIElp1 depletion from trigeminal placode cells leads to aberrant target tissue innervation and disrupts proper neural crest-placodal neuron interactions in the trigeminal ganglion. C_LI Grant sponsor and numberNIH R01DE024217 and NIH R03HD108480.