Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain.

Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain.
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DOI:
10.1088/1478-3975/9/6/066007
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发表时间:
2012-12
期刊:
影响因子:
2
通讯作者:
Taber LA
Taber LA
中科院分区:
生物学4区
文献类型:
--
作者:
Filas BA;Oltean A;Majidi S;Bayly PV;Beebe DC;Taber LA

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在胚胎早期,大脑最初形成一个由神经干细胞组成的相对直的圆柱形上皮管。然后,脑管分成三个主要的囊泡(前脑、中脑、后脑),以及后脑的一系列凸起(斜形囊)。这些分支之间的边界作为差异基因表达区域已经得到了很好的研究,但是产生这些收缩的形态发生机制还没有得到很好的理解。在这里,我们发现肌动球蛋白的收缩性的区域差异在胚胎鸡脑的囊泡形成中起主要作用。特别是,在暴露于非肌肉肌球蛋白II抑制剂blebbistatin的大脑中,边界没有形成,而使用calyculin或ATP增加收缩力则大大加深了边界。组织染色显示收缩可能发生在壁内侧,因为f -肌动蛋白和磷酸化的肌球蛋白集中在顶端侧。然而,相对较少的肌动蛋白和肌凝蛋白被发现在菱形球边界。为了确定驱动囊泡形成的具体物理机制,我们开发了脑管的有限元模型。在模型中模拟了区域顶端收缩,通过收缩蛋白分布和细胞形状测量来估计收缩各向异性和强度。该模型表明,结合边界区域的周向收缩和边界之间的相对各向同性收缩可以产生真实的初级囊泡形态。相反,菱形球的形成可能涉及边界之间的纵向收缩。进一步的模拟表明,这些不同的机制是由初始形态的区域差异和承受脑脊液压力的需要决定的。本研究为早期脑形态发生提供了新的认识。
In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood. Here, we show that regional variations in actomyosin-based contractility play a major role in vesicle formation in the embryonic chicken brain. In particular, boundaries did not form in brains exposed to the nonmuscle myosin II inhibitor blebbistatin, whereas increasing contractile force using calyculin or ATP deepened boundaries considerably. Tissue staining showed that contraction likely occurs at the inner part of the wall, as F-actin and phosphorylated myosin are concentrated at the apical side. However, relatively little actin and myosin was found in rhombomere boundaries. To determine the specific physical mechanisms that drive vesicle formation, we developed a finite-element model for the brain tube. Regional apical contraction was simulated in the model, with contractile anisotropy and strength estimated from contractile protein distributions and measurements of cell shapes. The model shows that a combination of circumferential contraction in the boundary regions and relatively isotropic contraction between boundaries can generate realistic morphologies for the primary vesicles. In contrast, rhombomere formation likely involves longitudinal contraction between boundaries. Further simulations suggest that these different mechanisms are dictated by regional differences in initial morphology and the need to withstand cerebrospinal fluid pressure. This study provides a new understanding of early brain morphogenesis.
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