Marsh-Armstrong Nicholas, Cai Liquan, Brown Donald D
Department of Neuroscience, Johns Hopkins University School of Medicine, and Kennedy Krieger Institute, 707 North Broadway Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):165-70. doi: 10.1073/pnas.2136755100. Epub 2003 Dec 22.
During premetamorphic stages, Xenopus laevis tadpoles expressing either a dominant-negative thyroid hormone (TH) receptor or a type-III iodothyronine deiodinase transgene in the nervous system have reduced TH-induced proliferation in the spinal cord and produce fewer hindlimb-innervating motorneurons. During prometamorphic stages, innervation of the hindlimbs is reduced, and few functional neuromuscular connections are formed. By metamorphic climax, limb movement is impaired, ranging from uncoordinated leg swimming to complete quadriplegia. This phenotype is due to transgene action in the tadpole spinal cord. The requirement of TH for neurogenesis during premetamorphosis is the earliest TH-regulated process reported to date in the sequence of metamorphic changes in anurans. The muscle formed during limb growth was previously shown to be a direct target of TH control. Here, we show that the same is true of the development of spinal cord cells that innervate the limbs.
在变态前阶段,在神经系统中表达显性负性甲状腺激素(TH)受体或III型碘甲状腺原氨酸脱碘酶转基因的非洲爪蟾蝌蚪,其脊髓中TH诱导的增殖减少,并且产生的支配后肢的运动神经元较少。在变态前阶段,后肢的神经支配减少,并且几乎没有形成功能性神经肌肉连接。到变态高潮时,肢体运动受损,从不协调的腿部游泳到完全四肢瘫痪不等。这种表型是由于转基因在蝌蚪脊髓中的作用。变态前神经发生对TH的需求是迄今为止在无尾两栖动物变态变化序列中报道的最早受TH调节的过程。先前已表明肢体生长过程中形成的肌肉是TH控制的直接靶标。在这里,我们表明支配肢体的脊髓细胞的发育也是如此。