Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development

Abstract

Summary: The somatotopic motor-neuron projections onto their cognate target muscles are essential for coordinated movement, but how that occurs for facial motor circuits, which have critical roles in respiratory and interactive behaviors, is poorly understood. We report extensive molecular heterogeneity in developing facial motor neurons in the mouse and identify markers of subnuclei and the motor pools innervating specific facial muscles. Facial subnuclei differentiate during migration to the ventral hindbrain, where neurons with progressively later birth dates—and evolutionarily more recent functions—settle in more-lateral positions. One subpopulation marker, ETV1, determines both positional and target muscle identity for neurons of the dorsolateral (DL) subnucleus. In Etv1 mutants, many markers of DL differentiation are lost, and individual motor pools project indifferently to their own and neighboring muscle targets. The resulting aberrant activation patterns are reminiscent of the facial synkinesis observed in humans after facial nerve injury. : Tenney et al. demonstrate that embryonic facial motor neurons are transcriptionally diverse as they establish somatotopic innervation of the facial muscles, a process that requires the transcription factor ETV1. Facial-motor axon-targeting errors in Etv1 mutants cause coordination of whisking and eyeblink evocative of human blepharospasm. Keywords: cranial nerve, facial nerve, facial nucleus, motor neuron, somatotopy, ETV1, axon guidance, neuronal migration, synkinesis, motor pool