Defining the Role of Integrins in Melanoblast Migration In Vivo.

IF 2.7 3区 生物学 Q3 CELL BIOLOGY
Wenjun Deng, Guy Tanentzapf
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引用次数: 0

Abstract

During embryonic development, neural crest-derived melanoblasts, which are precursors of pigment-producing melanocytes, disperse throughout the skin by long-range cell migration that requires adhesion to the ECM. Members of the integrin family of cell-ECM adhesion receptors are thought to contribute to melanocyte migration in vitro. However, due to the functional redundancy between different integrin heterodimers, the precise role of integrins in melanoblast migration, as well as the mechanisms that regulate them in this process, especially in in vivo contexts, remain poorly understood. To address this, we utilize the existing transcriptomic databases to identify different integrin subunits that are specifically expressed in melanoblasts, melanocytes and melanoma cancer cell lines. We then use mouse embryonic skin explants combined with drug and small molecule-based perturbations to target different integrins as well as specific mechanisms that modulate integrin activity. Individual melanoblasts from live imaging movies are tracked using high-resolution, quantitative, automated analysis, and cell morphology, cell migration and actin-based protrusions are analyzed. Overall, we uncover the non-redundant roles of different integrin heterodimers and elucidate the function of outside-in integrin activation in melanoblasts. Finally, we describe the function played, in vivo, by integrin-mediated adhesion to specific ECM ligands during melanoblast migration. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

整合素在体内黑色素细胞迁移中的作用。
在胚胎发育过程中,神经嵴来源的黑素母细胞是产生色素的黑素细胞的前体,通过远距离细胞迁移分散在整个皮肤中,这需要粘附到ECM上。细胞- ecm粘附受体的整合素家族成员被认为有助于体外黑素细胞迁移。然而,由于不同整合素异源二聚体之间的功能冗余,整合素在成黑细胞迁移中的确切作用,以及在这一过程中调节它们的机制,特别是在体内环境中,仍然知之甚少。为了解决这个问题,我们利用现有的转录组数据库来鉴定在黑色素母细胞、黑色素细胞和黑色素瘤癌细胞系中特异性表达的不同整合素亚基。然后,我们使用小鼠胚胎皮肤外植体结合药物和基于小分子的扰动来靶向不同的整合素以及调节整合素活性的特定机制。使用高分辨率,定量,自动化分析跟踪实时成像电影中的单个黑素母细胞,并分析细胞形态,细胞迁移和基于肌动蛋白的突起。总的来说,我们揭示了不同整合素异源二聚体的非冗余作用,并阐明了外内向整合素激活在黑素母细胞中的功能。最后,我们描述了在黑色素细胞迁移过程中,整合素介导的特异性ECM配体粘附在体内所起的作用。[媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本][媒体:看到文本]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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