A role for midbrain arcs in nucleogenesis
A role for midbrain arcs in nucleogenesis
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DOI：
10.1242/dev.00179
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
Ragsdale, CW
中科院分区：
文献类型：
--
作者：
Agarwala, S;Ragsdale, CW
细胞核是脊椎动物脑组织的基本单位，但它们在发育过程中产生的机制仍不清楚。一种可能性是，脑组织早期形成的重复区域（如神经节和神经柱）的模式有助于将神经元分配给不同的核命运。我们在鸡胚腹侧中脑中测试了这种可能性，在那里，分子上不同的条纹（中脑弧）的周期性图案先于中脑核的出现。我们发现中脑弧的形成与核团的形成有直接的关系。这两个差异同源异型盒基因表达和诊断轴突追踪研究建立了最内侧弧包含两个主要的中脑核团的原基：眼神经复合体和红核。我们通过在Sonic Hedgehog和FGF8错误表达实验中扰动弧图案形成来测试内侧弧与眼神经复合体和红核5779发育的关系。我们发现，诱导异位弧或扩大正常弧模式的Sonic Hedgehog操作引起红核和oculornotor复合体原基的精确平行诱导或扩张。我们进一步发现，FGF8操纵，推动内侧弧吻协调移动红核和oculornotor复合体原基。总之，这些发现表明，弧代表了一种模式化机制，中脑祖细胞被分配到特定的核命运。
Nuclei are fundamental units of vertebrate brain organization, but the mechanisms by which they are generated in development remain unclear. One possibility is that the early patterning of brain tissue into reiterated territories such as neuromeres and columns serves to allocate neurons to distinct nuclear fates. We tested this possibility in chick embryonic ventral midbrain, where a periodic pattern of molecularly distinct stripes (midbrain arcs) precedes the appearance of midbrain nuclei. We found that midbrain arc patterning has a direct relationship to the formation of nuclei. Both differential homeobox gene expression and diagnostic axon tracing studies established that the most medial arc contains primordia for two major midbrain nuclei: the oculomotor complex and the red nucleus. We tested the relationship of the medial arc to oculomotor complex and red nucleus 5779 development by perturbing arc pattern formation in Sonic Hedgehog and FGF8 misexpression experiments. We found that Sonic Hedgehog manipulations that induce ectopic arcs or expand the normal arc pattern elicit precisely parallel inductions or expansions of the red nucleus and oculornotor complex primordia. We further found that FGF8 manipulations that push the medial arc rostrally coordinately move both the red nucleus and oculornotor complex anlagen. Taken together, these findings suggest that arcs represent a patterning mechanism by which midbrain progenitor cells are allocated to specific nuclear fates.