Planar cell polarity (PCP), the orientation and alignment of cells within a sheet, is a ubiquitous cellular property that is commonly governed by the conserved set of proteins encoded by so-called ...PCP genes. The PCP proteins coordinate developmental signaling cues with individual cell behaviors in a wildly diverse array of tissues. Consequently, disruptions of PCP protein functions are linked to defects in axis elongation, inner ear patterning, neural tube closure, directed ciliary beating, and left/right patterning, to name only a few. This review attempts to synthesize what is known about PCP and the PCP proteins in vertebrate animals, with a particular focus on the mechanisms by which individual cells respond to PCP cues in order to execute specific cellular behaviors.
Multiciliated Cells Brooks, Eric R.; Wallingford, John B.
CB/Current biology,
10/2014, Volume:
24, Issue:
19
Journal Article
Peer reviewed
Open access
Cilia are microtubule-based projections that serve a wide variety of essential functions in animal cells. Defects in cilia structure or function have recently been found to underlie diverse human ...diseases. While many eukaryotic cells possess only one or two cilia, some cells, including those of many unicellular organisms, exhibit many cilia. In vertebrates, multiciliated cells are a specialized population of post-mitotic cells decorated with dozens of motile cilia that beat in a polarized and synchronized fashion to drive directed fluid flow across an epithelium. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite their importance, multiciliated cells are relatively poorly studied and we are only beginning to understand the mechanisms underlying their development and function. Here, we review the general phylogeny and physiology of multiciliation and detail our current understanding of the developmental and cellular events underlying the specification, differentiation and function of multiciliated cells in vertebrates.
Eric Brooks and John B. Wallingford review the development, function and phylogenetic distribution of multiciliated cells.
Planar cell polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple ...global cues, including gradients of gene expression, gradients of secreted WNT ligands and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking and degradation dynamics of PCP components further regulate planar tissue patterning. This polarization propagates throughout the whole tissue, providing a polarity axis that governs collective morphogenetic events such as the orientation of subcellular structures and cell rearrangements. Reflecting the necessity of polarized cellular behaviours for proper development and function of diverse organs, defects in PCP have been implicated in human pathologies, most notably in severe birth defects.
Despite our understanding of actomyosin function in individual migrating cells, we know little about the mechanisms by which actomyosin drives collective cell movement in vertebrate embryos. The ...collective movements of convergent extension drive both global reorganization of the early embryo and local remodeling during organogenesis. We report here that planar cell polarity (PCP) proteins control convergent extension by exploiting an evolutionarily ancient function of the septin cytoskeleton. By directing septin-mediated compartmentalization of cortical actomyosin, PCP proteins coordinate the specific shortening of mesenchymal cell-cell contacts, which in turn powers cell interdigitation. These data illuminate the interface between developmental signaling systems and the fundamental machinery of cell behavior and should provide insights into the etiology of human birth defects, such as spina bifida and congenital kidney cysts.
Cell motility is a widespread biological property that is best understood in the context of individual cell migration. Indeed, studies of migration in culture have provided tremendous insight into ...the signals and mechanics involved and have laid the foundation for our understanding of similar migrations by larger cellular collectives. By contrast, our understanding of another flavor of movement, cell intercalation during convergent extension, is only now emerging. Here, we integrate divergent findings related to intercalation in different settings into a unifying model, paying attention to how this model does and does not resemble current models for directed cell migration.
Huebner and Wallingford present a Perspective to describe the connection between directed individual cell migration and cell intercalation during convergent extension. They describe the cell biological underpinnings of both processes and their similarities and differences.
A general principle of biology is the self‐assembly of proteins into functional complexes. Characterizing their composition is, therefore, required for our understanding of cellular functions. ...Unfortunately, we lack knowledge of the comprehensive set of identities of protein complexes in human cells. To address this gap, we developed a machine learning framework to identify protein complexes in over 15,000 mass spectrometry experiments which resulted in the identification of nearly 7,000 physical assemblies. We show our resource, hu.MAP 2.0, is more accurate and comprehensive than previous state of the art high‐throughput protein complex resources and gives rise to many new hypotheses, including for 274 completely uncharacterized proteins. Further, we identify 253 promiscuous proteins that participate in multiple complexes pointing to possible moonlighting roles. We have made hu.MAP 2.0 easily searchable in a web interface (http://humap2.proteincomplexes.org/), which will be a valuable resource for researchers across a broad range of interests including systems biology, structural biology, and molecular explanations of disease.
SYNOPSIS
Integration of orthogonal high‐throughput mass spectrometry datasets using a machine learning framework reveals nearly 7,000 human protein assemblies and offers insights into novel protein function.
Hu.MAP 2.0 represents the most accurate and comprehensive human protein complex map available to date.
It indicates potential functions for 274 completely uncharacterized proteins.
It identifies 253 proteins that participate in multiple complexes suggesting multi‐functionality.
A searchable web resource is available at humap2.proteincomplexes.org.
Integration of orthogonal high‐throughput mass spectrometry datasets using a machine learning framework reveals nearly 7,000 human protein assemblies and offers insights into novel protein function.
Planar cell polarity signaling governs a wide array of polarized cell behaviors in animals. Recent reports now show that PCP signaling is essential for the directional beating of motile cilia. ...Interestingly, PCP signaling acts in a variety of ciliated cell types that use motile cilia to generate directional fluid flow in very different ways. This review will synthesize these recent papers and place them in context with previous studies of PCP signaling in polarized cellular morphogenesis and collective cell movement.
Humans have sought to understand the embryo for millennia. Paradoxically, even as technical and intellectual innovations bring us ever closer to a transformative understanding of developmental ...biology, our discipline faces an “image problem.” We should face this problem by acknowledging that developmental biology is fundamental to the human experience.
Humans have sought to understand the embryo for millennia. Paradoxically, even as technical and intellectual innovations bring us ever closer to a transformative understanding of developmental biology, our discipline faces an “image problem.” We should face this problem by acknowledging that developmental biology is fundamental to the human experience.
Morpholinos: Antisense and Sensibility Blum, Martin; De Robertis, Edward M.; Wallingford, John B. ...
Developmental cell,
10/2015, Volume:
35, Issue:
2
Journal Article
Peer reviewed
Open access
For over 15 years, antisense morpholino oligonucleotides (MOs) have allowed developmental biologists to make key discoveries regarding developmental mechanisms in numerous model organisms. Recently, ...serious concerns have been raised as to the specificity of MO effects, and it has been recommended to discontinue their usage, despite the long experience of the scientific community with the MO tool in thousands of studies. Reviewing the many advantages afforded by MOs, we conclude that adequately controlled MOs should continue to be accepted as generic loss-of-function approach, as otherwise progress in developmental biology will greatly suffer.
For over 15 years, antisense morpholino oligonucleotides (MOs) have allowed developmental biologists to make key discoveries regarding developmental mechanisms in numerous model organisms. Recently, serious concerns have been raised as to the specificity of MO effects, and it has been recommended to discontinue their usage, despite the long experience of the scientific community with the MO tool in thousands of studies. Reviewing the many advantages afforded by MOs, we conclude that adequately controlled MOs should continue to be accepted as generic loss-of-function approach, as otherwise progress in developmental biology will greatly suffer.
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