Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development
Alan P. Tenney,
Jean Livet,
Timothy Belton,
Michaela Prochazkova,
Erica M. Pearson,
Mary C. Whitman,
Ashok B. Kulkarni,
Elizabeth C. Engle,
Christopher E. Henderson
Affiliations
Alan P. Tenney
Center for Motor Neuron Biology and Disease (MNC), Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Corresponding author
Jean Livet
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
Timothy Belton
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
Michaela Prochazkova
Functional Genomics Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA
Erica M. Pearson
Center for Motor Neuron Biology and Disease (MNC), Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA
Mary C. Whitman
Department of Ophthalmology, Boston Children’s Hospital/Harvard Medical School, Boston, MA 02115, USA
Ashok B. Kulkarni
Functional Genomics Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA
Elizabeth C. Engle
Department of Neurology, Boston Children’s Hospital/Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Boston Children’s Hospital/Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
Christopher E. Henderson
Center for Motor Neuron Biology and Disease (MNC), Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative (CSCI), Columbia University, New York, NY 10032, USA; Columbia Translational Neuroscience Initiative (CTNI), Columbia University, New York, NY 10032, USA; Department of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Neurology, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA
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
