Retinoic acid, an essential component of the roof plate organizer, promotes the spatiotemporal segregation of dorsal neural fates.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2024-10-01 Epub Date: 2024-09-30 DOI:10.1242/dev.202973
Dina Rekler, Shai Ofek, Sarah Kagan, Gilgi Friedlander, Chaya Kalcheim
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引用次数: 0

Abstract

Dorsal neural tube-derived retinoic acid promotes the end of neural crest production and transition into a definitive roof plate. Here, we analyze how this impacts the segregation of central and peripheral lineages, a process essential for tissue patterning and function. Localized in ovo inhibition in quail embryos of retinoic acid activity followed by single-cell transcriptomics unraveled a comprehensive list of differentially expressed genes relevant to these processes. Importantly, progenitors co-expressed neural crest, roof plate and dI1 interneuron markers, indicating a failure in proper lineage segregation. Furthermore, separation between roof plate and dI1 interneurons is mediated by Notch activity downstream of retinoic acid, highlighting their crucial role in establishing the roof plate-dI1 boundary. Within the peripheral branch, where absence of retinoic acid resulted in neural crest production and emigration extending into the roof plate stage, sensory progenitors failed to separate from melanocytes, leading to formation of a common glia-melanocyte cell with aberrant migratory patterns. In summary, the implementation of single-cell RNA sequencing facilitated the discovery and characterization of a molecular mechanism responsible for the segregation of dorsal neural fates during development.

视黄酸是顶板组织器的重要组成部分,能促进背侧神经命运的时空分离。
背神经管衍生的视黄酸可促进神经嵴生成的结束并过渡到最终的顶板。在此,我们分析了这一过程如何影响中枢和外周系的分离,这一过程对组织形态和功能至关重要。在鹌鹑胚胎中局部抑制视黄酸活性,然后进行单细胞转录组学研究,揭示了与这些过程相关的差异表达基因的综合列表。重要的是,祖细胞共同表达了神经嵴、顶板和dI1中间神经元标记,这表明神经嵴、顶板和dI1中间神经元未能正确分离。此外,顶板和 dI1 中间神经元之间的分离是由视黄酸下游的 Notch 活动介导的,这突出了它们在建立顶板-dI1 边界中的关键作用。在外周分支中,视黄酸的缺失导致神经嵴的生成和迁移延伸到顶板阶段,感觉祖细胞未能与黑色素细胞分离,从而形成了具有异常迁移模式的神经胶质-黑色素细胞共同细胞。scRNA测序的实施共同促进了背侧神经在发育过程中命运分离的分子机制的发现和特征描述。
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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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