Short-range Fgf signalling patterns hindbrain progenitors to induce the neurogenesis-to-oligodendrogenesis switch.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY Development Pub Date : 2024-11-22 DOI:10.1242/dev.204256
Tim J Yeung, David G Wilkinson
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Abstract

In the vertebrate nervous system, neurogenesis generally precedes gliogenesis. The mechanisms driving the switch in cell type production and generation of the correct proportion of cell types remain unclear. Here, we show that Fgf20 signalling patterns progenitors to induce the switch from neurogenesis to oligodendrogenesis in the zebrafish hindbrain. Fgf20 emanating from earlier-born neurons signals at a short range to downregulate proneural gene expression in the segment centre with high spatial precision along both anterior-posterior (AP) and dorsal-ventral (DV) axes. This signal induces oligodendrocytes in the segment centre by upregulating olig2 and sox10 expression in pre-patterned competent progenitors. We show that the magnitude of proneural gene downregulation and the quantity of OPCs specified is dependent on the extent of Fgf20 signalling. Overexpression of fgf20a induces precocious specification and differentiation of oligodendrocytes among olig2+ progenitors, resulting in an increase in oligodendrocytes at the expense of neurogenesis. Thus, Fgf20 signalling defines the proportion of each cell type produced. Taken together, Fgf20 signalling from earlier-born neurons patterns hindbrain segments spatially and temporally to induce the neurogenesis-to-oligodendrogenesis switch.

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短程 Fgf 信号为后脑祖细胞提供模式,诱导神经发生向孤树突发生的转换。
在脊椎动物的神经系统中,神经发生通常先于胶质细胞发生。驱动细胞类型生成和正确比例细胞类型生成转换的机制仍不清楚。在这里,我们展示了 Fgf20 信号在斑马鱼后脑中诱导祖细胞从神经发生向少突胶质细胞发生转换的模式。来自早期出生的神经元的 Fgf20 信号可在短距离内沿前后(AP)轴和背腹(DV)轴高度精确地下调节段中心的神经元基因表达。这种信号通过上调有能力的前模式祖细胞中 olig2 和 sox10 的表达,诱导节段中心的少突胶质细胞。我们的研究表明,proneural 基因下调的幅度和指定的 OPC 数量取决于 Fgf20 信号的程度。过量表达 fgf20a 会诱导少突胶质细胞在少突2+祖细胞中过早分化,从而导致少突胶质细胞的增加,而神经元的生成则会受到影响。因此,Fgf20 信号决定了每种细胞类型产生的比例。综上所述,来自早先出生的神经元的Fgf20信号在空间和时间上对后脑节段进行模式化,从而诱导神经发生向少突胶质细胞发生的转换。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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