Early microglia progenitors colonize the embryonic CNS via integrin-mediated migration from the pial surface.

IF 8.7 1区 生物学 Q1 CELL BIOLOGY
Philippe Petry, Alexander Oschwald, Simon Merkt, Thien-Ly Julia Dinh, Geoffroy Andrieux, Cylia Crisand, Hannah Botterer, Elisa Nent, Neil Paterson, Monique Havermans, Roman Sankowski, Oliver Schilling, Melanie Boerries, Lukas Amann, Olaf Groß, Andreas Schlitzer, Marco Prinz, Tim Lämmermann, Katrin Kierdorf
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引用次数: 0

Abstract

Macrophage progenitors colonize their anatomical niches in the central nervous system (CNS) in distinct pre- and postnatal waves. Microglia progenitors originate from early erythromyeloid progenitors in the yolk sac and enter the murine CNS around embryonic day (E)9.5. While their developmental origin is well established, the molecular mechanisms guiding CNS colonization are not yet resolved. Using transcriptomic and proteomic approaches, we identified potential factors involved in this process. Microglia progenitors showed a distinct integrin surface profile and transmigrate along the extracellular matrix (ECM)-enriched pial surface into the CNS, pointing to a mesenchyme-to-CNS migration route. Loss of the integrin adaptor protein talin-1 in microglia progenitors led to a reduced CNS colonization, whereas macrophage progenitors in the surrounding mesenchyme remained unchanged. Overall, our data suggest that microglial progenitors enter the CNS parenchyma via talin-1-mediated migration from the surrounding mesenchyme through the ECM-enriched pial surface.

Abstract Image

早期的小胶质细胞祖细胞通过整合素介导的从头部表面迁移到胚胎中枢神经系统。
巨噬细胞祖细胞在中枢神经系统(CNS)中以不同的产前和产后波定植其解剖壁龛。小胶质细胞祖细胞起源于卵黄囊内的早期红髓祖细胞,并在胚胎日左右进入小鼠中枢神经系统(E)9.5。虽然它们的发育起源已经确定,但指导中枢神经系统定植的分子机制尚未解决。利用转录组学和蛋白质组学方法,我们确定了参与这一过程的潜在因素。小胶质细胞祖细胞表现出明显的整合素表面轮廓,并沿着细胞外基质(ECM)富集的脑顶表面迁移到中枢神经系统,表明了间质到中枢神经系统的迁移途径。小胶质细胞祖细胞中整合素衔接蛋白talin-1的缺失导致中枢神经系统定植减少,而周围间质中的巨噬细胞祖细胞则保持不变。总的来说,我们的数据表明,小胶质细胞祖细胞通过talin-1介导的从周围间质通过富含ecm的脑顶表面迁移进入中枢神经系统实质。
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来源期刊
Developmental cell
Developmental cell 生物-发育生物学
CiteScore
18.90
自引率
1.70%
发文量
203
审稿时长
3-6 weeks
期刊介绍: Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.
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