Nguyen V H, Trout J, Connors S A, Andermann P, Weinberg E, Mullins M C
University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, 421 Curie Blvd, Philadelphia, PA 19104-6058, USA.
Development. 2000 Mar;127(6):1209-20. doi: 10.1242/dev.127.6.1209.
We have studied the role of Bmp signaling in patterning neural tissue through the use of mutants in the zebrafish that disrupt three different components of a Bmp signaling pathway: swirl/bmp2b, snailhouse/bmp7 and somitabun/smad5. We demonstrate that Bmp signaling is essential for the establishment of the prospective neural crest and dorsal sensory Rohon-Beard neurons of the spinal cord. Moreover, Bmp signaling is necessary to limit the number of intermediate-positioned lim1+ interneurons of the spinal cord, as observed by the dramatic expansion of these prospective interneurons in many mutant embryos. Our analysis also suggests a positive role for Bmp signaling in the specification of these interneurons, which is independent of Bmp2b/Swirl activity. We found that a presumptive ventral signal, Hh signaling, acts to restrict the amount of dorsal sensory neurons and trunk neural crest. This restriction appears to occur very early in neural tissue development, likely prior to notochord or floor plate formation. A similar early role for Bmp signaling is suggested in the specification of dorsal neural cell types, since the bmp2b/swirl and bmp7/snailhouse genes are only coexpressed during gastrulation and within the tail bud, and are not found in the dorsal neural tube or overlying epidermal ectoderm. Thus, a gastrula Bmp2b/Swirl and Bmp7/Snailhouse-dependent activity gradient may not only act in the specification of the embryonic dorsoventral axis, but may also function in establishing dorsal and intermediate neuronal cell types of the spinal cord.
我们通过利用斑马鱼中的突变体研究了骨形态发生蛋白（Bmp）信号在神经组织模式形成中的作用，这些突变体破坏了Bmp信号通路的三个不同组分：swirl/bmp2b、snailhouse/bmp7和somitabun/smad5。我们证明Bmp信号对于脊髓中预期神经嵴和背侧感觉罗霍恩-比尔兹神经元的建立至关重要。此外，正如在许多突变胚胎中观察到的这些预期中间神经元的显著扩张所表明的那样，Bmp信号对于限制脊髓中位于中间位置的lim1+中间神经元的数量是必要的。我们的分析还表明Bmp信号在这些中间神经元的特化中具有积极作用，这独立于Bmp2b/Swirl活性。我们发现一种假定的腹侧信号，即音猬因子（Hh）信号，起到限制背侧感觉神经元和躯干神经嵴数量的作用。这种限制似乎在神经组织发育的非常早期就发生了，可能在脊索或底板形成之前。在背侧神经细胞类型的特化中也暗示了Bmp信号有类似的早期作用，因为bmp2b/swirl和bmp7/snailhouse基因仅在原肠胚形成期间和尾芽内共表达，而在背侧神经管或覆盖的表皮外胚层中未发现。因此，原肠胚期依赖Bmp2b/Swirl和Bmp7/Snailhouse的活性梯度可能不仅在胚胎背腹轴的特化中起作用，还可能在脊髓背侧和中间神经元细胞类型的建立中发挥作用。
