Aurora-A Breaks Symmetry in Contractile Actomyosin Networks Independently of Its Role in Centrosome Maturation

1. Download high-res image (214KB)
2. Download full-size image

     

Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking

Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.     

Symmetry breaking and polarity establishment during mouse oocyte maturation

Mammalian oocyte meiosis encompasses two rounds of asymmetric divisions to generate a totipotent haploid egg and, as by-products, two small polar bodies. Two intracellular events, asymmetric spindle positioning and cortical polarization, are critical to such asymmetric divisions. Actin but not microtubule cytoskeleton has been known to be directly involved in both events. Recent work has revealed a positive feedback loop between chromosome-mediated cortical activation and the Arp2/3-orchestrated cytoplasmic streaming that moves chromosomes. This feedback loop not only maintains meiotic II spindle position during metaphase II arrest, but also brings about symmetry breaking during meiosis I. Prior to an Arp2/3-dependent phase of fast movement, meiotic I spindle experiences a slow and non-directional first phase of migration driven by a pushing force from Fmn2-mediated actin polymerization. In addition to illustrating these molecular mechanisms, mathematical simulations are presented to elucidate mechanical properties of actin-dependent force generation in this system.     

Injection of myo-inositol reverses the effects of lithium on sea urchin blastomeres

Lithium is known to cause sea urchin blastomeres destined to give rise to epithelium rather than to differentiate into gut or skeleton. While it has been proposed that lithium alters development by interfering with the inositol-tris phosphate-protein kinase C (IP₃-PKC) signaling pathway, the mechanism of action of lithium in sea urchins has remained elusive. Here we describe experiments that examine the hypothesis that lithium exerts its effect on sea urchin embryos via the IP₃-PKC pathway. We make use of methods developed to isolate epithelial precursor cells from the animal hemisphere of cleavage 16-cell stage embryos. Pairs of cells were isolated and one of each pair was injected with either myo-inositol or its inactive isomer, epi-inositol. Rhodamine dextran was co-injected as a lineage tracer to follow the fate of injected cells. We demonstrate that injected myo-inositol, but not epi-inositol, can reverse the effects of lithium on sea urchin blastomeres. This is direct evidence that lithium affects the IP₃-PKC pathway in sea urchins, and that this pathway plays an important role in cell fate determination.     

Symmetry Breaking by Spontaneous Crystallization – Is it the Most Plausible Source of Terrestrial Handedness we have Long Been Looking for? – A Reappraisal

In the light of recent and controversial findings on spontaneous resolution of racemates and their implications in the origin of homochirality on earth, we present here a detailed review of this important topic. Although spontaneous resolution cannot at this moment be reliably predicted, there has also been considerable progress in crystal structure prediction and, not only thermodynamic factors, but also kinetic ones, play important roles in the efficiency of packing and crystallization. In addition, self-association and supramolecular control phenomena may be identified in cases where spontaneous resolution of enantiomers is actually occurring. While this contribution summarizes our current understanding of this intriguing phenomena, it is hoped that future work on crystalline conglomerates (or homochiral crystals) of prebiotic importance will be of further help to understand the general problem of terrestrial chirogenesis.     

Patterning of the avian intermediate mesoderm by lateral plate and axial tissues

Amniote kidney tissue is derived from the intermediate mesoderm (IM), a strip of mesoderm that lies between the somites and the lateral plate. While much has been learned concerning the later events which regulate the differentiation of IM into tubules and other types of kidney tissue, much less is known concerning the earlier events which regulate formation of the IM itself. In the current study, the chick pronephros was used as a model system to identify tissues that play a role in patterning the IM and the critical time periods during which such patterning events take place. Explant studies revealed that the prospective pronephric IM is already specified to express kidney genes by stage 6, shortly after its gastrulation through the primitive streak, and earlier than previously reported. Transplant and explant experiments revealed that the lateral plate contains an activity that can repress IM formation in tissues that are already specified to express IM genes. In contrast, Hensen's node can promote formation of IM in the lateral plate. Paraxial tissues (presomitic mesoderm plus neural plate and notochord) were found to influence the morphogenesis of the nephric duct, but did not induce IM tissue to an appreciable extent. Combining lateral plate and paraxial tissue in vivo or in vitro led to induction of IM genes in the paraxial mesoderm but not in the lateral plate mesoderm. Based on these results and those of others, we propose a two-step model for the patterning of the IM. While tissue is still in the primitive streak, the prospective IM is relatively uncommitted. By stage 6, shortly after cells leave the primitive streak, a field of cells is generate which is specified to give rise to IM (Step 1). Subsequently, competing signals from the lateral plate and axial tissues modulate the number of cells that commit to an IM fate (Step 2).     

心脏的起源和细胞谱系

心脏是器官发生过程中最早形成的结构之一.心脏的原基分布图和心脏细胞谱系是心脏起源和形态发生研究的主要方面.总结了近几年来以鸡和小鼠为模型,在心脏发生和心脏前体细胞定位方面的研究情况.