Wright D E, White F A, Gerfen R W, Silos-Santiago I, Snider W D
Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Comp Neurol. 1995 Oct 16;361(2):321-33. doi: 10.1002/cne.903610209.
The protein collapsin was purified from chick brain on the basis of its ability to inhibit sensory neuron growth cones, implicating this molecule in sensory axon guidance (Luo et al. [1993] Cell 75:217-227). To examine the relationship between collapsin and sensory axon growth, we examined the pattern of mRNA expression of collapsin's mammalian paralogue, Semaphorin III (Sema III), and compared it to dorsal root ganglion (DRG) axon pathways in the developing rat embryo. Centrally, DRG axons enter the spinal cord by embryonic (E) 11 and branch into the gray matter by E15 in brachial and thoracic regions. Laminar specific targets are reached by E17. Between E13 and E17, Sema III mRNA is expressed at high levels in the entire ventral half of the spinal cord except the floor plate. This pattern suggests that Sema III may inhibit non-proprioceptive sensory axons from penetrating the ventral spinal cord. Peripherally, sensory axons have entered the anterior sclerotome by E11 at all rostrocaudal levels. At this age, Sema III mRNA is already expressed in the dermamyotome and ventral aspect of the posterior sclerotome, areas which axons pass between but do not penetrate en route to their peripheral targets. From E12 to E15, the axons lengthen and branch into smaller fascicles which extend toward peripheral targets. During this time, Sema III mRNA is expressed by many mesodermal structures surrounding the axon fascicles, with highest levels observed in the dermamyotome, perinotochordal mesenchyme, pelvic girdle, and limb. As development proceeds, Sema III mRNA expression is quickly downregulated before disappearing by birth. Taken together, our results demonstrate that the gene for Sema III is expressed in central and peripheral regions which are avoided by growing DRG axons. These findings are consistent with the idea that Sema III inhibits growth and branching of axons into inappropriate areas during development.
蛋白塌陷素是根据其抑制感觉神经元生长锥的能力从鸡脑中纯化出来的，这表明该分子参与感觉轴突导向（Luo等人[1993]《细胞》75:217 - 227）。为了研究塌陷素与感觉轴突生长之间的关系，我们检测了塌陷素的哺乳动物同源物信号素III（Sema III）的mRNA表达模式，并将其与发育中的大鼠胚胎背根神经节（DRG）轴突通路进行比较。在中枢，DRG轴突在胚胎期（E）11进入脊髓，并在E15时在臂部和胸部区域分支进入灰质。在E17时到达层特异性靶点。在E13和E17之间，Sema III mRNA在脊髓整个腹侧半部高水平表达，但底板除外。这种模式表明Sema III可能抑制非本体感觉性感觉轴突穿透腹侧脊髓。在周围，感觉轴突在E11时已在所有头尾水平进入前体节。在这个年龄，Sema III mRNA已在皮肌节和后体节腹侧表达，轴突在到达外周靶点的途中经过这些区域但不穿透。从E12到E15，轴突延长并分支成更小的束，向外周靶点延伸。在此期间，Sema III mRNA由围绕轴突束的许多中胚层结构表达，在皮肌节、脊索周围间充质、骨盆带和肢体中观察到最高水平。随着发育进行，Sema III mRNA表达在出生前迅速下调然后消失。综合来看，我们的结果表明Sema III基因在生长中的DRG轴突避开的中枢和外周区域表达。这些发现与Sema III在发育过程中抑制轴突生长和分支进入不适当区域的观点一致。
