title: Dlk1 promotes a fast motor neuron biophysical signature required for peak force execution.
abstract: 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 ~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.
authors.affiliation: Developmental Neurobiology Laboratory, European Neuroscience Institute (ENI-G), Grisebachstraße 5, 37077 Göttingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Müller
authors.forename: Pitchaiah
authors.initials: P
authors.lastname: Cherukuri
authors.forename: Kristine
authors.initials: K
authors.lastname: Henningfeld
authors.forename: Chor Hoon
authors.initials: CH
authors.lastname: Poh
authors.forename: Lars
authors.initials: L
authors.lastname: Wittler
authors.forename: Phillip
authors.initials: P
authors.lastname: Grote
authors.forename: Oliver
authors.initials: O
authors.lastname: Schlüter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schmidt
authors.forename: Jorge
authors.initials: J
authors.lastname: Laborda
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bauer
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brownstone
authors.forename: Till
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009068:Movement; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C587235:Kcng4 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D051880:Receptors, Notch