Ren Tianbo, Zhang Jiangyang, Plachez Celine, Mori Susumu, Richards Linda J
Department of Anatomy and Neurobiology and The Program in Neuroscience, The University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Neurosci. 2007 Sep 26;27(39):10345-9. doi: 10.1523/JNEUROSCI.2787-07.2007.
In many cases of callosal dysgenesis in both human patients and mouse models, misguided fibers from the cortex form abnormal bilateral, barrel-shaped structures known as Probst bundles. Because little is known about how axons are arranged within these anomalous fiber bundles, understanding this arrangement may provide structural and molecular insights into how axons behave when they are misguided in vivo. Previous studies described these bundles as longitudinal swirls of axons that fail to cross the midline (Ozaki et al., 1987). However, recent studies on human acallosal patients using diffusion tensor magnetic resonance imaging (DTMRI) technology suggest that axons project in an anteroposterior direction within the Probst bundle (Lee et al., 2004; Tovar-Moll et al., 2007). This led us to ask the question, is DTMRI an accurate method for analyzing axonal tracts in regions of high axon overlap and disorganization, or is our current perception of axon arrangement within these bundles inaccurate? Using DTMRI, immunohistochemistry, and carbocyanine dye tract-tracing studies, we analyzed the Probst bundles in both Netrin1 and deleted in colorectal cancer (DCC) mutant mice. Our findings indicate that DTMRI can accurately demonstrate fiber tract orientation and morphology where axons are in ordered arrays such as in the dorsal part of the bundle. In ventral areas, where the axons are disorganized, no coordinated diffusion is apparent via DTMRI. In these regions, a higher-resolution approach such as tract tracing is required. We conclude that in DCC and Netrin1 mutant mice, guidance mechanisms remain in the dorsal part of the tract but are lost ventrally.
在人类患者和小鼠模型的许多胼胝体发育不全病例中，来自皮质的错误导向纤维形成了异常的双侧桶状结构，称为普罗布斯特束。由于对轴突在这些异常纤维束中的排列方式知之甚少，了解这种排列方式可能会为轴突在体内被错误导向时的行为提供结构和分子层面的见解。先前的研究将这些束描述为未能穿过中线的轴突纵向漩涡（尾崎等人，1987年）。然而，最近对无胼胝体人类患者使用扩散张量磁共振成像（DTMRI）技术的研究表明，轴突在普罗布斯特束内沿前后方向投射（李等人，2004年；托瓦尔 - 莫尔等人，2007年）。这使我们提出一个问题，DTMRI是分析轴突高度重叠和紊乱区域中轴突束的准确方法吗？还是我们目前对这些束内轴突排列的认识不准确？我们使用DTMRI、免疫组织化学和羰花青染料束路追踪研究，分析了Netrin1和结直肠癌缺失（DCC）突变小鼠中的普罗布斯特束。我们的研究结果表明，DTMRI能够准确显示轴突呈有序排列区域（如束的背侧部分）的纤维束方向和形态。在轴突紊乱的腹侧区域，通过DTMRI没有明显的协调扩散。在这些区域，需要更高分辨率的方法，如束路追踪。我们得出结论，在DCC和Netrin1突变小鼠中，导向机制在束的背侧部分仍然存在，但在腹侧丧失。
