Establishment and expression of cellular polarity in fucoid zygotes.

Zygotes of fucoid algae have long been studied as a paradigm for cell polarity. Polarity is established early in the first cell cycle and is then expressed as localized growth and invariant cell division. The fertilized egg is a spherical cell and, by all accounts, bears little or no asymmetry. Polarity is acquired epigenetically a few hours later in the form of a rhizoid/thallus axis. The initial stage of polarization is axis selection, during which zygotes monitor environment gradients to determine the appropriate direction for rhizoid formation. In their natural setting in the intertidal zone, sunlight is probably the most important polarizing vector; rhizoids form away from the light. The mechanism by which zygotes perceive environmental gradients and transduce that information into an intracellular signal is unknown but may involve a phosphatidylinositol cycle. Once positional information has been recorded, the cytoplasm and membrane are reorganized in accordance with the vectorial information. The earliest detectable asymmetries in the polarizing zygote are localized secretion and generation of a transcellular electric current. Vesicle secretion and the inward limb of the current are localized at the presumptive rhizoid. The transcellular current may establish a cytoplasmic Ca2+ gradient constituting a morphogenetic field, but this remains controversial. Localized secretion and establishment of transcellular current are sensitive to treatment with cytochalasins, indicating that cytoplasmic reorganization is dependent on the actin cytoskeleton. The nascent axis at first is labile and susceptible to reorientation by subsequent environmental vectors but soon becomes irreversibly fixed in its orientation. Locking the axis in place requires both cell wall and F-actin and is postulated to involve an indirect transmembrane bridge linking cortical actin to cell wall. This bridge anchors relevant structures at the presumptive rhizoid and thereby stabilizes the axis. Approximately halfway through the first cell cycle, the latent polarity is expressed morphologically in the form of rhizoid growth. Elongation is by tip growth and does not appear to be fundamentally different from tip growth in other organisms. The zygote always divides perpendicular to the growth axis, and this is controlled by the microtubule cytoskeleton. Two microtubule-organizing centers on the nuclear envelope rotate such that they align with the growth axis. They then serve as spindle poles during mitosis. Cytokinesis bisects the axial spindle, resulting in a transverse crosswall. Although the chronology of cellular events associated with polarity is by now rather detailed, causal mechanisms remain obscure.     

Where does asymmetry come from? Illustrating principles of polarity and asymmetry establishment in Drosophila neuroblasts

Asymmetric cell division (ACD) is the fundamental process through which one cell divides into two cells with different fates. In animals, it is crucial for the generation of cell-type diversity and for stem cells, which use ACD both to self-renew and produce one differentiating daughter cell. One of the most prominent model systems of ACD, Drosophila neuroblasts, relies on the PAR complex, a conserved set of proteins governing cell polarity in animals. Here, we focus on recent advances in our understanding of the mechanisms that control the orientation of the neuroblast polarity axis, how the PAR complex is positioned, and how its activity may regulate division orientation and cell fate determinant localization and discuss how important findings about the composition polarity complexes in other models may apply to neuroblasts.     

RNA sorting in Xenopus oocytes and embryos.

Cytoplasmic localization of mRNA molecules has emerged as a powerful mechanism for generating spatially restricted gene expression. This process is an important contributor to cell polarity in both somatic cells and oocytes, and can provide the basis for patterning during embryonic development. In vertebrates, this phenomenon is perhaps best documented in the frog, Xenopus laevis, where polarity along the animal-vegetal axis coincides with the localization of numerous mRNA molecules. Research over the last several years has made exciting progress toward understanding the molecular mechanisms underlying cytoplasmic mRNA localization.     

Cell flow and tissue polarity patterns

Planar tissue polarity is a fundamental feature of many epithelia. Large-scale cell polarity patterns govern the orientation of external structures such as hairs and cilia. Tissue polarity patterns arise from the collective organization of cells, which are polarized individually. Such cell and tissue polarities are reflected in anisotropic distributions of proteins of the planar cell polarity (PCP) pathway. Here we give an overview on recent progress in understanding how large-scale patterns of tissue polarity are controlled. We highlight the role of active mechanical events in the organization of polarity patterns during the development of the pupal fly wing. Patterns of cell flow are generated by mechanical stresses exerted on the tissue as well as by oriented cell divisions and neighbor exchanges. We discuss how the resulting tissue shear controls polarity orientation. We argue that the often-observed alignment of PCP either parallel or perpendicular to the long axis of developing tissues is a characteristic consequence of shear-induced polarity alignment. This principle allows for the versatile and robust generation of polarity patterns in tissues.     

Cell division orientation and planar cell polarity pathways

The orientation of cell division has a crucial role in early embryo body plan specification, axis determination and cell fate diversity generation, as well as in the morphogenesis of tissues and organs. In many instances, cell division orientation is regulated by the planar cell polarity (PCP) pathways: the Wnt/Frizzled non-canonical pathway or the Fat/Dachsous/Four-jointed pathway. Firstly, using asymmetric cell division in both Drosophila and C. elegans, we describe the central role of the Wnt/Frizzled pathway in the regulation of asymmetric cell division orientation, focusing on its cooperation with either the Src kinase pathway or the heterotrimeric G protein pathway. Secondly, we describe our present understanding of the mechanisms by which the planar cell polarity pathways drive tissue morphogenesis by regulating the orientation of symmetric cell division within a field of cells. Finally, we will discuss the important avenues that need to be explored in the future to better understand how planar cell polarity pathways control embryo body plan determination, cell fate specification or tissue morphogenesis by mitotic spindle orientation.     

Ontogenesis in the Fucophyceae: case studies and comparison of fucoid zygotes and Sphacelaria apical cells

In multicellular eukaryotes, the zygote, a single cell, gives rise to the different cell types of the organism. The study of the mechanisms involved is a key point of developmental biology. Generally, the first stages are characterized by an orderly sequence of asymmetrical divisions resulting from an initial developmental polarity. The establishment of this initial polarity has been the subject of numerous studies in animals, but not in higher plants since the zygote is encased in several layers of tissues that prevent experimental approaches. Moreover, plant development is characterized by two successive ontogenetic steps: the construction of the embryonic apico-basal axis and the establishment of meristems in charge of organogenesis. Members of the Fucophyceae provide good models for the investigation of these processes. Any inferred homology of mechanisms must take into account the polyphyletic nature of the algae. This paper is a tentative review of two case studies: fucoid zygotes and Sphacelaria apical cells, and deals respectively with the two successive ontogenetic steps characteristic of higher plant development. The first part concerns development of the fucoid zygotes. Fucoid zygotes, including those of different species, are considered as model systems in plants for studying the establishment of the polarity axis because, at the moment of fertilization, they do not have any morphological or biochemical polarity. This report concerns progress in the identification of some cellular or molecular mechanisms involved in the settlement and/or stabilization of the polarity axis, and the consequence of this polar organisation for the control of asymmetrical divisions and the building of a functional embryo. The second part concerns the apical cell of Sphacelaria as a model for establishing and maintaining a meristematic cell. The apical cell exhibits a permanent polarized organisation throughout repetitive asymmetric divisions and can be comparatively analysed in situ and isolated as a protoplast. This allowed us to investigate the evolution of the cytoplasmic cytoskeleton, centrosomes and the mitotic apparatus during the cell cycle in relation to the cell polarity; particularly the interactions between the cytoskeleton and cell wall. For the two models, the results are compared with mechanisms involved in the development of other multicellular organisms, and their value in gaining an insight into higher plant ontogenesis is assessed.     

Progress and challenges in understanding planar cell polarity signaling

During development, epithelial cells in some tissues acquire a polarity orthogonal to their apical–basal axis. This polarity, referred to as planar cell polarity (PCP), or tissue polarity, is essential for the normal physiological function of many epithelia. Early studies of PCP focused on insect epithelia (Lawrence, 1966 [1]), and the earliest genetic analyses were carried out in Drosophila (Held et al., 1986; Gubb and Garcia-Bellido, 1982 [2,3]). Indeed, most of our mechanistic understanding of PCP derives from the ongoing use of Drosophila as a model system. However, a range of medically important developmental defects and physiological processes are under the control of PCP mechanisms that appear to be at least partially conserved, driving considerable interest in studying PCP both in Drosophila and in vertebrate model systems. Here, I present a model of the PCP signaling mechanism based on studies in Drosophila. I highlight two areas in which our understanding is deficient, and which lead to current confusion in the literature. Future studies that shed light on these areas will substantially enhance our understanding of the fascinating yet challenging problem of understanding the mechanisms that generate PCP.     

Cell polarity, auxin transport, and cytoskeleton-mediated division planes: who comes first?

In plants, cell polarity is an issue more recurring than in other systems, because plants, due to their adaptive and flexible development, often change cell polarity postembryonically according to intrinsic cues and demands of the environment. Recent findings on the directional movement of the plant signalling molecule auxin provide a unique connection between individual cell polarity and the establishment of polarity at the tissue, organ, and whole-plant levels. Decisions about the subcellular polar targeting of PIN auxin transport components determine the direction of auxin flow between cells and consequently mediate multiple developmental events. In addition, mutations or chemical interference with PIN-based auxin transport result in abnormal cell divisions. Thus, the complicated links between cell polarity establishment, auxin transport, cytoskeleton, and oriented cell divisions now begin to emerge. Here we review the available literature on the issues of cell polarity in both plants and animals to extend our understanding on the generation, maintenance, and transmission of cell polarity in plants.     

Cell polarity: intrinsic or externally imposed?

A basic question in studies of the genesis of cell polarity is whether the polarity is an intrinsic and permanent property of cells or whether it is externally imposed by signals at the cell periphery. Current models favor the possibility that an external signal selectively imposes a polarized cell morphology. However, recent data from different experimental systems are discussed here that support the idea that an intrinsic polarity in animal cells is maintained through a dynamic process involving specific activities of the cortical microfilament system and the centrosome-microtubule complex. In this view, external signals capable of modulating cell polarity, for example, during chemotaxis or histogenesis, do so by acting on mechanisms that maintain cells permanently polarized. The contribution of the cytoskeleton to the genesis of cell polarity is discussed, with particular reference to experimental evidence for global cytoskeletal dynamics, and it is suggested that critical advances in our understanding of the maintenance of cell polarity will depend on our obtaining further knowledge of the molecular mechanisms controlling interactions between microtubules and microfilaments. Microtubules appear to exert an inhibitory control on the recruitment of cytoplasmic myosin into the cortex, and there are data indicating that the centrosome and centrioles could actively contribute to the establishment of cell polarity.     

Multiple levels of regulation specify the polarity of an asymmetric cell division in C. elegans

Wnt signaling systems play important roles in the generation of cell and tissue polarity during development. We describe a Wnt signaling system that acts in a new way to orient the polarity of an epidermal cell division in C. elegans. In this system, the EGL-20/Wnt signal acts in a permissive fashion to polarize the asymmetric division of a cell called V5. EGL-20 regulates this polarization by counteracting lateral signals from neighboring cells that would otherwise reverse the polarity of the V5 cell division. Our findings indicate that this lateral signaling pathway also involves Wnt pathway components. Overexpression of EGL-20 disrupts both the asymmetry and polarity of lateral epidermal cell divisions all along the anteroposterior (A/P) body axis. Together our findings suggest that multiple, inter-related Wnt signaling systems may act together to polarize asymmetric cell divisions in this tissue.     

The polarising role of cell adhesion molecules in early development

Polarising a cell or an embryo is a crucial and recurrent event during development, as it is important for cell differentiation and migration. Cells can become polarised along their apical-basal axis and also within the plane of the tissue layer to which they belong. The embryo develops three axes: the anteroposterior, the dorsoventral and the left-right axis. Recent work indicates instructive roles for cell adhesion molecules in establishing not only apical-basal polarity but also planar cell polarity and, surprisingly, in the generation of left-right asymmetry in vertebrates. Signalling cascades that regulate polarity formation seem to be conserved among different organisms, thereby raising the intriguing question of whether this also holds true for the cell adhesion molecules.     

Pole position: How plant cells polarize along the axes

Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.

This review discusses the principles, mechanisms, and evolution of plant cell polarity, an essential cellular feature for plant development and physiology that endows cells with a sense of direction.     

Establishment and Maintenance of Cell Polarity During Leukocyte Chemotaxis

The term polarity refers to the differential distribution of the macromolecular elements of a cell, resulting in its asymmetry in function, shape and/or content. Polarity is a fundamental property of all metazoan cells in at least some stages, and is pivotal to processes such as epithelial differentiation (apical/basal polarity), coordinated cell activity within the plane of a tissue (planar cell polarity), asymmetric cell division, and cell migration. In the last case, an apparently symmetric cell responds to directional cues provided by chemoattractants, creating a polarity axis that runs from the cell anterior, or leading edge, in which actin polymerization takes place, to the cell posterior (termed uropod in leukocytes), in which acto-myosin contraction occurs. Here we will review some of the molecular mechansisms through which chemoattractants break cell symmetry to trigger directed migration, focusing on cells of the immune system. We briefly highlight some common or apparently contradictory pathways reported as important for polarity in other cells, as this suggests conserved or cell type-specific mechanisms in eukaryotic cell chemotaxis.     

Establishment and Maintenance of Cell Polarity During Leukocyte Chemotaxis

The term polarity refers to the differential distribution of the macromolecular elements of a cell, resulting in its asymmetry in function, shape and/or content. Polarity is a fundamental property of all metazoan cells in at least some stages, and is pivotal to processes such as epithelial differentiation (apical/basal polarity), coordinated cell activity within the plane of a tissue (planar cell polarity), asymmetric cell division, and cell migration. In the last case, an apparently symmetric cell responds to directional cues provided by chemoattractants, creating a polarity axis that runs from the cell anterior, or leading edge, in which actin polymerization takes place, to the cell posterior (termed uropod in leukocytes), in which acto-myosin contraction occurs. Here we will review some of the molecular mechanisms through which chemoattractants break cell symmetry to trigger directed migration, focusing on cells of the immune system. We briefly highlight some common or apparently contradictory pathways reported as important for polarity in other cells, as this suggests conserved or cell type-specific mechanisms in eukaryotic cell chemotaxis.Key Words: chemotaxis, polarization, lipid rafts, signaling, cytoskeleton     

Human Embryonic Stem Cell-Derived Neurons as a Tool for Studying Neuroprotection and Neurodegeneration

The capacity to generate myriad differentiated cell types, including neurons, from human embryonic stem (hES) cell lines offers great potential for developing cell-based therapies and also for increasing our understanding of human developmental mechanisms. In addition, the emerging development of this technology as an experimental tool represents a potential opportunity for neuroscientists interested in mechanisms of neuroprotection and neurodegeneration. Potentially unlimited generation of well-defined functional neurons from hES and patient-specific induced pluripotent cells offers new systems to study disease mechanisms, signalling pathways and receptor pharmacology within a human cellular environment. Such systems may help in overcoming interspecies differences. Far from replacing rodent in vivo and primary culture systems, hES and induced disease-specific pluripotent stem cell-derived neurons offer a complementary resource to overcome issues of interspecies differences, accelerate drug discovery, study of disease mechanism and provide basic insight into human neuronal physiology.     

Morphogenetic fields in embryogenesis, regeneration, and cancer: Non-local control of complex patterning

Establishment of shape during embryonic development, and the maintenance of shape against injury or tumorigenesis, requires constant coordination of cell behaviors toward the patterning needs of the host organism. Molecular cell biology and genetics have made great strides in understanding the mechanisms that regulate cell function. However, generalized rational control of shape is still largely beyond our current capabilities. Significant instructive signals function at long range to provide positional information and other cues to regulate organism-wide systems properties like anatomical polarity and size control. Is complex morphogenesis best understood as the emergent property of local cell interactions, or as the outcome of a computational process that is guided by a physically encoded map or template of the final goal state? Here I review recent data and molecular mechanisms relevant to morphogenetic fields: large-scale systems of physical properties that have been proposed to store patterning information during embryogenesis, regenerative repair, and cancer suppression that ultimately controls anatomy. Placing special emphasis on the role of endogenous bioelectric signals as an important component of the morphogenetic field, I speculate on novel approaches for the computational modeling and control of these fields with applications to synthetic biology, regenerative medicine, and evolutionary developmental biology.     

Noble metal,oxide and chalcogenide-based nanomaterials from scalable phototrophic culture systems

Phototrophic cell or tissue cultures can produce nanostructured noble metals, oxides and chalcogenides at ambient temperatures and pressures in an aqueous environment and without the need for potentially toxic solvents or the generation of dangerous waste products. These “green” synthesized nanobiomaterials can be used to fabricate biosensors and bio-reporting tools, theranostic vehicles, medical imaging agents, as well as tissue engineering scaffolds and biomaterials. While successful at the lab and experimental scales, significant barriers still inhibit the development of higher capacity processes. While scalability issues in traditional algal bioprocess engineering are well known, such as the controlled delivery of photons and gas-exchange, the large-scale algal synthesis of nanomaterials introduces additional parameters to be understood, i.e., nanoparticle (NP) formation kinetics and mechanisms, biological transport of metal cations and the effect of environmental conditions on the final form of the NPs. Only after a clear understanding of the kinetics and mechanisms can the strain selection, photobioreactor type, medium pH and ionic strength, mean light intensity and other relevant parameters be specified for an optimal bioprocess. To this end, this mini-review will examine the current best practices and understanding of these phenomena to establish a path forward for this technology.     

Translating cell polarity into tissue elongation

Planar cell polarity, the orientation of single-cell asymmetries within the plane of a multicellular tissue, is essential to generating the shape and dimensions of organs and organisms. Planar polarity systems align cell behavior with the body axes and orient the cellular processes that lead to tissue elongation. Using Drosophila as a model system, significant progress has been made toward understanding how planar polarity is generated by biochemical and mechanical signals. Recent studies using time-lapse imaging reveal that cells engage in a number of active behaviors whose orientation and dynamics translate planar cell polarity into tissue elongation. Here we review recent progress in understanding the cellular mechanisms that link planar polarity to large-scale changes in tissue structure.     

Control of spindle polarity and orientation in Saccharomyces cerevisiae

Control of mitotic spindle orientation represents a major strategy for the generation of cell diversity during development of metazoans. Studies in the budding yeast Saccharomyces cerevisiae have contributed towards our present understanding of the general principles underlying the regulation of spindle positioning in an asymmetrically dividing cell. In S. cerevisiae, the mitotic spindle must orient along the cell polarity axis, defined by the site of bud emergence, to ensure correct nuclear division between the mother and daughter cells. Establishment of spindle polarity dictates this process and relies on the concerted control of spindle pole function and a precise program of cues originating from the cell cortex that directs cytoplasmic microtubule attachments during spindle morphogenesis. These cues cross talk with the machinery responsible for bud-site selection, indicating that orientation of the spindle in yeast cells is mechanistically coupled to the definition of a polarity axis and the division plane. Here, we propose a model integrating the inherently asymmetric properties of the spindle pathway with the program of positional information contributing towards orienting the spindle in budding yeast. Because the basic machinery orienting the spindle in higher-eukaryotic cells appears to be conserved, it might be expected that similar principles govern centrosome asymmetry in the course of metazoan development.