EphA4 and EfnB2a maintain rhombomere coherence by independently regulating intercalation of progenitor cells in the zebrafish neural keel.
EphA4 and EfnB2a maintain rhombomere coherence by independently regulating intercalation of progenitor cells in the zebrafish neural keel.
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DOI：
10.1016/j.ydbio.2008.12.010
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发表时间：
2009-03-15
影响因子：
2.7
通讯作者：
Moens, Cecilia B.
中科院分区：
文献类型：
--
作者：
Kemp, Hilary A.;Cooke, Julie E.;Moens, Cecilia B.
在脊椎动物的发育过程中，后脑暂时被分割成7个不同的菱形节（r）。后脑分割发生在神经形成所需的复杂形态发生的背景下，在斑马鱼中涉及一个特征性的跨中线分裂，在形成的神经管中双侧分布祖细胞。Eph受体酪氨酸激酶EphA 4和膜结合的Ephrin（Efn）配体EfnB 2a，在早期后脑中的互补片段中表达，是菱形边界形成所需的。我们先前表明，EphA 4促进r3和r5内的细胞-细胞亲和力，并提出菱形内的优先粘附有助于边界形成。在这里，我们表明，EfnB 2a是同样需要在r4的正常细胞亲和力和EphA 4和EfnB 2a调节细胞亲和力独立在各自的菱形。镶嵌胚胎细胞分选的实时成像显示，这两种蛋白质在后脑神经龙骨的跨中线细胞分裂过程中发挥作用。与此相一致的是，嵌合EfnB 2a过表达引起广泛的细胞分选并破坏后脑组织，但仅当在神经龙骨阶段或之前诱导时。我们提出了一个模型，在该模型中，Eph和Efn依赖的细胞亲和力在菱形节内的硬骨鱼神经形成的潜在破坏性过程中，用于维持菱形节组织。
During vertebrate development, the hindbrain is transiently segmented into 7 distinct rhombomeres (r). Hindbrain segmentation takes place within the context of the complex morphogenesis required for neurulation, which in zebrafish involves a characteristic cross-midline division that distributes progenitor cells bilaterally in the forming neural tube. The Eph receptor tyrosine kinase EphA4 and the membrane-bound Ephrin (Efn) ligand EfnB2a, which are expressed in complementary segments in the early hindbrain, are required for rhombomere boundary formation. We showed previously that EphA4 promotes cell-cell affinity within r3 and r5, and proposed that preferential adhesion within rhombomeres contributes to boundary formation. Here we show that EfnB2a is similarly required in r4 for normal cell affinity and that EphA4 and EfnB2a regulate cell affinity independently within their respective rhombomeres. Live imaging of cell sorting in mosaic embryos shows that both proteins function during cross-midline cell divisions in the hindbrain neural keel. Consistent with this, mosaic EfnB2a over-expression causes widespread cell sorting and disrupts hindbrain organization, but only if induced at or before neural keel stage. We propose a model in which Eph and Efn-dependent cell affinity within rhombomeres serve to maintain rhombomere organization during the potentially disruptive process of teleost neurulation.
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