Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary
Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary
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DOI：
10.1242/dev.186882
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发表时间：
2020-06-01
期刊：
影响因子：
4.6
通讯作者：
Brand, Michael
中科院分区：
文献类型：
--
作者：
Kesavan, Gokul;Machate, Anja;Brand, Michael
细胞群之间清晰边界的形成和维持在胚胎发育过程中起着至关重要的作用，因为它们将具有相似命运的细胞分隔开来。这些边界中的一些也充当组织者，具有诱导周围细胞中特定细胞命运和形态发生的能力。中脑-后脑边界（MHB）就是这样一个组织者：它作为一个谱系限制边界，以防止具有不同发育命运的细胞混合。然而，谱系限制过程的机制仍不清楚。在这里，使用新的荧光敲入报告，现场成像，Cre/lox介导的谱系追踪，原子力显微镜为基础的细胞粘附试验和突变体分析，我们分析了在MHB的谱系限制的过程，并提供机制的细节。具体来说，我们表明，谱系限制发生在原肠胚形成结束，并随后形成尖锐的基因表达边界的发展MHB发生通过互补机制，即细胞命运可塑性和细胞分选。此外，我们表明，在MHB细胞分选涉及不同的粘附中脑和后脑细胞，介导的N-钙粘蛋白和Eph-ephrin信号。
The formation and maintenance of sharp boundaries between groups of cells play a vital role during embryonic development as they serve to compartmentalize cells with similar fates. Some of these boundaries also act as organizers, with the ability to induce specific cell fates and morphogenesis in the surrounding cells. The midbrain-hindbrain boundary (MHB) is such an organizer: it acts as a lineage restriction boundary to prevent the intermingling of cells with different developmental fates. However, the mechanisms underlying the lineage restriction process remain unclear. Here, using novel fluorescent knockin reporters, live imaging, Cre/lox-mediated lineage tracing, atomic force microscopy-based cell adhesion assays and mutant analysis, we analyze the process of lineage restriction at the MHB and provide mechanistic details. Specifically, we show that lineage restriction occurs by the end of gastrulation, and that the subsequent formation of sharp gene expression boundaries in the developing MHB occur through complementary mechanisms, i.e. cell-fate plasticity and cell sorting. Furthermore, we show that cell sorting at the MHB involves differential adhesion among midbrain and hindbrain cells that is mediated by N-cadherin and Eph-ephrin signaling.