Innervation of cranial muscles requires Mllt11/Af1q/Tcf7c function during trigeminal ganglion development

Abstract

The development of cranial nerves, including the trigeminal nerve, and the formation of neuromuscular junctions (NMJs) are crucial processes for craniofacial motor function. Mllt11/Af1q/Tcf7c (henceforth Mllt11), a novel type of cytoskeletal-interacting protein, has been implicated in neuronal migration and neuritogenesis during central nervous system development. However, its role in peripheral nerve development and NMJ formation remains poorly understood. This study investigates the function of Mllt11 during trigeminal ganglion development and its impact on motor innervation of the masseter muscle. We report Mllt11 expression in the developing trigeminal ganglia, suggesting a potential role in cranial nerve development. Using a conditional knockout mouse model to delete Mllt11 in Wnt1-expressing neural crest cells, we assessed trigeminal ganglion development and innervation of the masseter muscle in the jaw. Surprisingly, we find that Mllt11 loss does not affect the initial formation of the trigeminal ganglion but disrupts its cellular composition, with a reduction in the ratio of neural crest-derived Sox10+ cells relative to placode-derived Isl1/2+ cells. Furthermore, our study demonstrates that conditional Mllt11 knockout leads to reduction of neurofilament density and NMJs within the masseter muscle, indicating altered trigeminal motor innervation. Our findings show that Mllt11 regulates the cellular composition of the trigeminal ganglion and is essential for proper trigeminal motor innervation in the masseter muscle.