Delta-Notch signaling and lateral inhibition in zebrafish spinal cord development.
Delta-Notch signaling and lateral inhibition in zebrafish spinal cord development.
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DOI：
10.1186/1471-213x-1-13
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发表时间：
2001
影响因子：
--
通讯作者：
Eisen JS
中科院分区：
文献类型：
--
作者：
Appel B;Givan LA;Eisen JS
脊椎动物神经发育需要细胞增殖和细胞规格的精确协调，以引导有丝分裂活性前体细胞有序转变为不同类型的有丝分裂后神经元和神经胶质细胞。由 Delta-Notch 信号通路介导的侧向抑制可能提供调节脊椎动物神经系统增殖和规范的机制。我们检查了斑马鱼胚胎中的 Delta 和 Notch 基因表达，并通过消融细胞和基因破坏 Delta-Notch 信号传导来测试侧向抑制在脊髓模式中的作用。斑马鱼胚胎在整个发育中的神经系统中表达多个 delta 和 notch 基因。所有或大多数增殖前体神经元似乎表达缺口基因，而前体神经元和有丝分裂后神经元的子集表达δ基因。当我们在初级运动神经元出生后不久消融它们时，它们就被替换了，这表明特定的神经元横向抑制邻近的前体神经元。 δ基因的突变导致躯干神经管的前体细胞过早停止分裂并发育为神经元。此外，突变胚胎具有过量的早期特定神经元，其命运适合其在神经管内的正常位置，并且伴随着晚期特定细胞的缺陷。我们的结果与新指定神经元表达的斑马鱼 Delta 蛋白促进邻近前体中 Notch 活性的观点一致。这种信号传导是维持增殖的前体细胞群并产生晚生神经元和神经胶质细胞所必需的。因此，Delta-Notch 信号传导可能通过协调细胞周期控制和细胞特化来使脊椎动物神经细胞的命运多样化。
Vertebrate neural development requires precise coordination of cell proliferation and cell specification to guide orderly transition of mitotically active precursor cells into different types of post-mitotic neurons and glia. Lateral inhibition, mediated by the Delta-Notch signaling pathway, may provide a mechanism to regulate proliferation and specification in the vertebrate nervous system. We examined delta and notch gene expression in zebrafish embryos and tested the role of lateral inhibition in spinal cord patterning by ablating cells and genetically disrupting Delta-Notch signaling. Zebrafish embryos express multiple delta and notch genes throughout the developing nervous system. All or most proliferative precursors appeared to express notch genes whereas subsets of precursors and post-mitotic neurons expressed delta genes. When we ablated identified primary motor neurons soon after they were born, they were replaced, indicating that specified neurons laterally inhibit neighboring precursors. Mutation of a delta gene caused precursor cells of the trunk neural tube to cease dividing prematurely and develop as neurons. Additionally, mutant embryos had excess early specified neurons, with fates appropriate for their normal positions within the neural tube, and a concomitant deficit of late specified cells. Our results are consistent with the idea that zebrafish Delta proteins, expressed by newly specified neurons, promote Notch activity in neighboring precursors. This signaling is required to maintain a proliferative precursor population and generate late-born neurons and glia. Thus, Delta-Notch signaling may diversify vertebrate neural cell fates by coordinating cell cycle control and cell specification.