title: Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles.
abstract: We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: Y W
authors.initials: YW
authors.lastname: Kwon
authors.forename: S J
authors.initials: SJ
authors.lastname: Abbondanzo
authors.forename: C L
authors.initials: CL
authors.lastname: Stewart
authors.forename: M E
authors.initials: ME
authors.lastname: Gurney
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009045:Motor Endplate; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
chemical_list: D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D053683:Oncostatin M