Determinants of motor neuron functional subtypes important for locomotor speed
Kristen P. D’Elia,
Hanna Hameedy,
Dena Goldblatt,
Paul Frazel,
Mercer Kriese,
Yunlu Zhu,
Kyla R. Hamling,
Koichi Kawakami,
Shane A. Liddelow,
David Schoppik,
Jeremy S. Dasen
Affiliations
Kristen P. D’Elia
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA
Hanna Hameedy
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA
Dena Goldblatt
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA; Center for Neural Science, New York University, New York, NY, USA
Paul Frazel
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA
Mercer Kriese
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA
Yunlu Zhu
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA
Kyla R. Hamling
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA
Koichi Kawakami
Laboratory of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan
Shane A. Liddelow
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA
David Schoppik
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA; Corresponding author
Jeremy S. Dasen
Department of Neuroscience & Physiology and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Corresponding author
Summary: Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.
