4.8 Article

Dlk1 Promotes a Fast Motor Neuron Biophysical Signature Required for Peak Force Execution

期刊

SCIENCE
卷 343, 期 6176, 页码 1264-1266

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1246448

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资金

  1. European Research Council under the European Union [311710 MU TUNING]
  2. Emmy-Noether Program of the Deutsche Forschungsgemeinschaft [MA4278/1-1]
  3. Center for Biologics Evaluation and Research, Food and Drug Administration
  4. Emmy-Noether Program [SCHL592-4]
  5. Canadian Institutes of Health Research
  6. Canada Research Chairs Program
  7. Canada Foundation for Innovation
  8. Nova Scotia Research and Innovation Trust
  9. Ministerio de Educacion y Ciencia, Spain

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Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from slow to fast, whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Here we identify the noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant of motor neuron functional diversification. Dlk1, expressed by similar to 30% of motor neurons, is necessary and sufficient to promote a fast biophysical signature in the mouse and chick. Dlk1 suppresses Notch signaling and activates expression of the K+ channel subunit Kcng4 to modulate delayed-rectifier currents. Dlk1 inactivation comprehensively shifts motor neurons toward slow biophysical and transcriptome signatures, while abolishing peak force outputs. Our findings provide insights into the development of motor neuron functional diversity and its contribution to the execution of movements.

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