The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis.

The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis.
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转录因子 Egr3 在肌梭形态发生过程中调节感觉轴突-肌管相互作用。

DOI:
10.1006/dbio.2001.0202
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发表时间:
2001
期刊:
Developmental biology.
影响因子:
--
通讯作者:
Kucera,J
Kucera,J
中科院分区:
--
文献类型:
--
作者:
Tourtellotte,WG;Keller-Peck,C;Milbrandt,J;Kucera,J

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锌指转录因子Egr家族由Egr 1、Egr 2、Egr 3和Egr 4组成,参与细胞生长和分化。成年Egr 3缺陷小鼠是共济失调的,并且缺乏通常在胚胎发育期间在Ia传入肌管接触部位发育的肌梭本体感受器。为了解决是否纺锤体的形式,然后退化,或者他们是否从来没有形成在Egr 3的情况下,我们研究了Egr 3相对于纺锤体发育的时空表达。在野生型小鼠中,Egr 3在发育中的肌管中表达后不久,他们受到神经支配的Ia传入和它的表达控制的神经支配,因为它消散后神经横断。在Egr 3缺陷小鼠,肌管接受Ia传入神经支配,并组装成纺锤体在胚胎发育过程中正常。然而,新生儿Egr 3缺陷纺锤体梭内纤维和薄囊内的内部肌核很少。此外,发育缓慢的肌球蛋白重链在胚胎Egr 3缺陷纺锤体中没有诱导,这表明在形态学上检测到它们之前存在分化障碍。出生后,感觉和运动神经支配从Egr3缺陷的纺锤体中撤出,纺锤体解体。尽管纺锤体解体,肌肉传入纤维回缩,但背根神经节内的本体感受神经元胞体仍保留下来。我们的结论是,Egr 3在调节未分化肌管转化为梭内纤维所需的基因,从而为纺锤体的表型分化中起着至关重要的作用。
The Egr family of zinc-finger transcription factors, consisting of Egr1, Egr2, Egr3, and Egr4, are involved in cellular growth and differentiation. Adult Egr3-deficient mice are ataxic and lack muscle spindle proprioceptors that normally develop at the sites of Ia afferent-myotube contacts during embryogenesis. To resolve whether spindles form and then degenerate, or whether they never form in the absence of Egr3, we examined the spatiotemporal expression of Egr3 relative to spindle development. In wild type mice, Egr3 was expressed in developing myotubes shortly after they were innervated by Ia afferents and its expression was controlled by innervation because it dissipated following nerve transection. In Egr3-deficient mice, myotubes received Ia afferent innervation and assembled normally into spindles during embryogenesis. However, newborn Egr3-deficient spindles had few internal myonuclei in intrafusal fibers and thin capsules. Moreover, slow-developmental myosin heavy chain was not induced in embryonic Egr3-deficient spindles suggesting that impairments in differentiation were present before they could be detected morphologically. After birth, sensory and motor innervation withdrew from the Egr3-deficient spindles, and the spindles disassembled. In spite of the spindle disassembly and retraction of afferents from muscles, the cell bodies of proprioceptive neurons within dorsal root ganglia were retained. We conclude that Egr3 has an essential role in regulating genes required for the transformation of undifferentiated myotubes into intrafusal fibers, and hence for the phenotypic differentiation of spindles.
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