Determinants of motor neuron functional subtypes important for locomotor speed

• Published in: Cell reports (Cambridge) 2023-09, Vol.42 (9), p.113049-113049, Article 113049
• Main Authors: D’Elia, Kristen P., Hameedy, Hanna, Goldblatt, Dena, Frazel, Paul, Kriese, Mercer, Zhu, Yunlu, Hamling, Kyla R., Kawakami, Koichi, Liddelow, Shane A., Schoppik, David, Dasen, Jeremy S.
• Format: Article
• Language: English
• Subjects: Animals; CP: Developmental biology; CP: Neuroscience; Locomotion; motor neuron; Motor Neurons - physiology; neural development; neural subtype; specification; Spinal Cord; transcription factor; Transcription Factors - genetics; Zebrafish
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113049

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. [Display omitted] •Larval zebrafish axial motor neurons have extensive molecular diversity•Fast motor neuron subtypes express the transcription factors Prdm16 and Mecom•Prdm16 and Mecom are required for fast motor neuron development•Motor neuron functional subtypes arise through intrinsic molecular programs D’Elia et al. define the molecular profiles of motor neurons essential for swimming speed control in zebrafish. They find that two transcription factors, Prdm16 and Mecom, are essential to specify motor neurons involved in fast locomotion. These results indicate that motor neuron functional subtypes are specified through intrinsic genetic programs.