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斑马鱼原肠胚的骨形态发生蛋白梯度通过调节细胞间黏附来引导外侧细胞迁移。

The Bmp gradient of the zebrafish gastrula guides migrating lateral cells by regulating cell-cell adhesion.

作者信息

von der Hardt Sophia, Bakkers Jeroen, Inbal Adi, Carvalho Lara, Solnica-Krezel Lilianna, Heisenberg Carl-Philipp, Hammerschmidt Matthias

机构信息

Max-Planck Institute of Immunobiology, D-79108 Freiburg, Germany.

出版信息

Curr Biol. 2007 Mar 20;17(6):475-87. doi: 10.1016/j.cub.2007.02.013. Epub 2007 Mar 1.

Abstract

BACKGROUND

Bone morphogenetic proteins (Bmps) are required for the specification of ventrolateral cell fates during embryonic dorsoventral patterning and for proper convergence and extension gastrulation movements, but the mechanisms underlying the latter role remained elusive.

RESULTS

Via bead implantations, we show that the Bmp gradient determines the direction of lateral mesodermal cell migration during dorsal convergence in the zebrafish gastrula. This effect is independent of its role during dorsoventral patterning and of noncanonical Wnt signaling. However, it requires Bmp signal transduction through Alk8 and Smad5 to negatively regulate Ca(2+)/Cadherin-dependent cell-cell adhesiveness. In vivo, converging mesodermal cells form lamellipodia that attach to adjacent cells. Bmp signaling diminishes the Cadherin-dependent stability of such contact points, thereby abrogating subsequent cell displacement during lamellipodial retraction.

CONCLUSIONS

We propose that the ventral-to-dorsal Bmp gradient has an instructive role to establish a reverse gradient of cell-cell adhesiveness, thereby defining different migratory zones and directing lamellipodia-driven cell migrations during dorsal convergence in lateral regions of the zebrafish gastrula.

摘要

背景

在胚胎背腹模式形成过程中,骨形态发生蛋白(Bmps)对于腹外侧细胞命运的特化以及原肠胚形成期适当的汇聚延伸运动是必需的,但后者作用的潜在机制仍不清楚。

结果

通过珠粒植入实验,我们发现Bmp梯度决定了斑马鱼原肠胚背侧汇聚过程中外侧中胚层细胞迁移的方向。这种作用独立于其在背腹模式形成过程中的作用以及非经典Wnt信号传导。然而,它需要通过Alk8和Smad5进行Bmp信号转导,以负向调节Ca(2+)/钙黏蛋白依赖性细胞间黏附。在体内,汇聚的中胚层细胞形成附着于相邻细胞上的片状伪足。Bmp信号传导降低了此类接触点的钙黏蛋白依赖性稳定性,从而消除了片状伪足回缩过程中随后的细胞位移。

结论

我们提出,从腹侧到背侧的Bmp梯度具有指导作用,可建立细胞间黏附的反向梯度,从而在斑马鱼原肠胚外侧区域的背侧汇聚过程中定义不同的迁移区域并引导片状伪足驱动的细胞迁移。

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