Rodino-Klapac Louise R, Beattie Christine E
Center for Molecular Neurobiology, The Ohio State University, Columbus, OH 43210, USA.
Dev Biol. 2004 Sep 15;273(2):308-20. doi: 10.1016/j.ydbio.2004.06.007.
Zebrafish primary motor axons extend along stereotyped pathways innervating distinct regions of the developing myotome. During development, these axons make stereotyped projections to ventral and dorsal myotome regions. Caudal primary motoneurons, CaPs, pioneer axon outgrowth along ventral myotomes; whereas, middle primary motoneurons, MiPs, extend axons along dorsal myotomes. Although the development and axon outgrowth of these motoneurons has been characterized, cues that determine whether axons will grow dorsally or ventrally have not been identified. The topped mutant was previously isolated in a genetic screen designed to uncover mutations that disrupt primary motor axon guidance. CaP axons in topped mutants fail to enter the ventral myotome at the proper time, stalling at the nascent horizontal myoseptum, which demarcates dorsal from ventral axial muscle. Later developing secondary motor nerves are also delayed in entering the ventral myotome whereas all other axons examined, including dorsally projecting MiP motor axons, are unaffected in topped mutants. Genetic mosaic analysis indicates that Topped function is non-cell autonomous for motoneurons, and when wild-type cells are transplanted into topped mutant embryos, ventromedial fast muscle are the only cell type able to rescue the CaP axon defect. These data suggest that Topped functions in the ventromedial fast muscle and is essential for motor axon outgrowth into the ventral myotome.
斑马鱼的初级运动轴突沿着定型路径延伸，支配发育中的肌节的不同区域。在发育过程中，这些轴突向腹侧和背侧肌节区域进行定型投射。尾侧初级运动神经元（CaP）引导轴突沿着腹侧肌节生长；而中间初级运动神经元（MiP）则沿着背侧肌节延伸轴突。尽管这些运动神经元的发育和轴突生长已得到描述，但决定轴突是向背侧还是腹侧生长的线索尚未确定。topped突变体先前是在一个旨在发现破坏初级运动轴突导向的突变的遗传筛选中分离出来的。topped突变体中的CaP轴突未能在适当时间进入腹侧肌节，在新生的水平肌隔处停滞，该肌隔将背侧和腹侧轴向肌肉区分开来。较晚发育的次级运动神经进入腹侧肌节也会延迟，而所有其他检测的轴突，包括向背侧投射的MiP运动轴突，在topped突变体中不受影响。遗传镶嵌分析表明，Topped功能对运动神经元是非细胞自主的，当将野生型细胞移植到topped突变体胚胎中时，腹内侧快肌是唯一能够挽救CaP轴突缺陷的细胞类型。这些数据表明，Topped在腹内侧快肌中起作用，并且对于运动轴突向腹侧肌节的生长至关重要。
