Recombinant Sea Urchin Vascular Endothelial Growth Factor Directs Single-Crystal Growth and Branching in Vitro

Recombinant Sea Urchin Vascular Endothelial Growth Factor Directs Single-Crystal Growth and Branching in Vitro
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DOI:
10.1021/ja309024b
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发表时间:
2012-10-31
影响因子:
15
通讯作者:
Joester, Derk
Joester, Derk
中科院分区:
化学1区
文献类型:
--
作者:
Knapp, Regina T.;Wu, Ching-Hsuan;Joester, Derk

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海胆胚胎中的生物矿化是一个晶体生长过程,导致具有复杂分支形状和光滑弯曲表面的定向单晶针状体。独特的是,构建内骨骼的原代间充质细胞(PMC)可以在体外培养。然而,在胚胎中的其他细胞分泌的形态发生线索的情况下,沉积在PMC培养物中的骨针缺乏在胚胎中观察到的复杂的分支行为。在这里,我们证明了重组海胆血管内皮生长因子(rVEGF),与细胞表面受体相互作用的信号分子,诱导骨针形成和控制骨针形状PMC文化。根据rVEGF的浓度,PMC沉积存款线性,“h”和“H”形,或三辐射针状。值得注意的是,从线性到三辐射的变化发生在从平行于方解石c轴的双向晶体生长到沿着三个a轴生长的切换。这一发现对我们理解细胞如何在多微米尺度上整合形态发生,并在原子尺度上控制晶格取向具有重要意义。PMC模型系统是唯一适合于研究这一机制,并开发生物技术方法的单晶生长。
Biomineralization in sea urchin embryos is a crystal growth process that results in oriented single-crystalline spicules with a complex branching shape and smoothly curving surfaces. Uniquely, the primary mesenchyme cells (PMCs) that construct the endoskeleton can be cultured in vitro. However, in the absence of morphogenetic cues secreted by other cells in the embryo, spicules deposited in PMC culture lack the complex branching behavior observed in the embryo. Herein we demonstrate that recombinant sea urchin vascular endothelial growth factor (rVEGF), a signaling molecule that interacts with a cell-surface receptor, induces spiculogenesis and controls the spicule shape in PMC culture. Depending on the rVEGF concentration, PMCs deposit linear, "h"- and "H"-shaped, or triradiate spicules. Remarkably, the change from linear to triradiate occurs with a switch from bidirectional crystal growth parallel to the calcite c axis to growth along the three a axes. This finding has implications for our understanding of how cells integrate morphogenesis on the multi-micrometer scale with control over lattice orientation on the atomic scale. The PMC model system is uniquely suited to investigate this mechanism and develop biotechnological approaches to single-crystal growth.