Kwon Y W, Abbondanzo S J, Stewart C L, Gurney M E
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Neurobiol. 1995 Sep;28(1):35-50. doi: 10.1002/neu.480280105.
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.
我们发现白血病抑制因子（LIF）在新生肌肉突触的程序性消退中发挥生理作用。首先，LIF mRNA存在于胚胎骨骼肌中，并受到发育调控。我们在胚胎第17天（E17）的小鼠后腿肌肉中检测到高水平的LIF mRNA。LIF mRNA的含量在E17和出生之间下降了10倍，然后在新生儿和成年期保持低水平。骨骼肌中LIF mRNA的减少与继发性肌生成的结束和成年肌纤维数量的完成相吻合。其次，从出生开始用LIF（100 ng/天）处理小鼠后腿的表浅肌肉阔筋膜张肌（TFL），可使多神经元支配的肌纤维中多余输入的消退暂时延迟约3天。该过程的中点从7.5±10.2±0.6日龄发生了变化。LIF处理通过改变其时间来延迟突触消退，而对其速率没有明显影响。第三，在LIF基因破坏的纯合小鼠中，多重支配的TFL肌纤维减少的中点提前1天出现，在6.5±0.5日龄。LIF基因敲除小鼠的肌纤维数量没有变化。用LIF处理不会改变新生儿的生长速率、TFL中的肌纤维数量或已消除的输入的重新出现。相反，LIF似乎通过暂时延迟突触消退的开始来延迟运动单位的成熟。我们假设这是一个选择性过程的必要组成部分，该过程将同时且平等地作用于多个相互竞争的运动单位。
