Early coordination of cell migration and cardiac fate determination during mammalian gastrulation.

Shayma Abukar,Peter A Embacher,Alessandro Ciccarelli,Sunita Varsani-Brown,Isabel G W North,Jamie A Dean,James Briscoe,Kenzo Ivanovitch
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Abstract

During gastrulation, mesodermal cells derived from distinct regions are destined to acquire specific cardiac fates after undergoing complex migratory movements. Here, we used light-sheet imaging of live mouse embryos between gastrulation and heart tube formation to track mesodermal cells and to reconstruct lineage trees and 3D migration paths for up to five cell divisions. We found independent progenitors emerging at specific times, contributing exclusively to left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tube's Nr2f2+ inflow tract during morphogenesis. We also identified short-lived multipotent progenitors with broad potential, illustrating early developmental plasticity. Descendants of multipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than the progeny of uni-fated progenitors. Progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations. In contrast, those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed down in comparison to LV/AVC cells. Together, these data reveal patterns of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.
哺乳动物原肠胚形成过程中细胞迁移和心脏命运决定的早期协调。
在原肠形成过程中,来自不同区域的中胚层细胞在经历复杂的迁移运动后,注定要获得特定的心脏命运。在这里,我们使用从原肠胚形成到心管形成之间的活小鼠胚胎的光片成像来跟踪中胚层细胞,并重建谱系树和多达五次细胞分裂的3D迁移路径。我们发现独立的祖细胞出现在特定的时间,专门贡献于左心室/房室管(LV/AVC)或心房肌细胞。LV/AVC祖细胞分化较早形成心新月形,而心房祖细胞在形态发生过程中较晚形成心管Nr2f2+流入道。我们还发现了具有广泛潜力的短命多能祖细胞,说明了早期发育可塑性。多能祖的后代比单能祖的后代在前中胚层内表现出更大的分散和更多样化的迁移轨迹。胚胎外中胚层(ExEm)的祖细胞迁移速度最快,分布最分散。相比之下,那些产生心内膜细胞、LV/AVC细胞和心包细胞的细胞表现出更渐进的分化,具有晚期行为转变:与LV/AVC细胞相比,心内膜细胞的速度增加,而心包细胞的速度减慢。总之,这些数据揭示了中胚层细胞看似无组织的迁移模式中的单个细胞方向性和心脏命运分配模式。
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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