Hot off the presses! Sep 15 Curr Biol

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Latest Articles Include:

• National health scare
  - Curr Biol 19(17):R715-R716 (2009)
  Mediawatch: Richard F. Harris looks at the response to the attack on Britain's National Health Service by American opponents of health reforms.
• Key data base
  - Curr Biol 19(17):R716-R717 (2009)
  Britain's health service may be under attack in the US but it is providing researchers with the base for a major health project. Nigel Williams reports.
• Bee mystery continues
  - Curr Biol 19(17):R718 (2009)
  As beekeepers continue to suffer serious colony losses, application of genomic tools reveals puzzling results. Michael Gross reports.
• Logging off
  - Curr Biol 19(17):R719-R720 (2009)
  The illegal removal and sale of tropical timber is one of the most damaging environmental problems, but a company has developed DNA techniques it hopes will better track trees' provenance. Nigel Williams reports.
• New elm hopes
  - Curr Biol 19(17):R720 (2009)
  A new project is hoping to help restore one devastated British tree. Nigel Williams reports.
• Species highs
  - Curr Biol 19(17):R721-R722 (2009)
  A new report highlights the threat of climate change to new species discovered in the eastern Himalayas over recent years, writes Nigel Williams.
• Kevin Padian
  - Curr Biol 19(17):R722-R723 (2009)
  
• The postsynaptic density
  - Curr Biol 19(17):R723-R724 (2009)
  
• Dancing to Darwin
  - Curr Biol 19(17):R725 (2009)
  
• Capturing plant intrigue
  - Curr Biol 19(17):R726 (2009)
  
• Contraction of body representation induced by proprioceptive conflict
  - Curr Biol 19(17):R727-R728 (2009)
  Our body is not only an extended object in external space, but also the basis of our sense of self. Proprioceptive signals from muscle spindle organs, specifying body position, play a key role in this unique dual quality of body representation, as they define a 'here' or set of locations, where 'I' am located [1]. Position information from muscle spindles can be manipulated by vibrating the muscle tendon, generating illusions of position and movement [2]. For example, biceps vibration generates illusions of elbow extension, while triceps vibration generates illusions of flexion. Here we report that proprioceptive conflict induced by simultaneous vibration of antagonistic biceps and triceps muscle tendons alters representation of the body in a way qualitatively different from single vibrations. Rather than relocation or movement, this incoherent conflict of location produces perceived telescoping of the arm towards the elbow. Loss of coherent information about b! ody position in space seems to produce contraction of the body representation itself. Our result suggests that basic sensory signals about body posture also play an essential role in representing the self as an extended object in space.
• Hedgehog Signalling: Kif7 Is Not That Fishy After All
  - Curr Biol 19(17):R729-R731 (2009)
  Recent reports examining the mammalian kinesin relative Kif7 highlight the conserved role for microtubule motor proteins in Drosophila and vertebrate Hedgehog signalling. Mammalian Kif7 action centres at the primary cilium, an organelle absent from Drosophila. These studies raise interesting questions about the coupling of microtubule trafficking to the Hedgehog pathway.
• Animal Cognition: Aesop's Fable Flies from Fiction to Fact
  - Curr Biol 19(17):R731-R732 (2009)
  A new study shows that rooks are able to spontaneously drop stones into a tube of water to obtain a floating worm. This sophisticated problem solving raises intriguing questions about the use of imagination in animals.
• DNA Distress: Just Ring 9-1-1
  - Curr Biol 19(17):R733-R734 (2009)
  The Rad9–Hus1–Rad1 checkpoint clamp (9-1-1) is a central player in the cellular response to DNA damage; three groups have determined the crystal structure of 9-1-1, providing new insight into its loading mechanism and association with DNA damage checkpoint and repair enzymes.
• Coevolutionary Biology: Sex and the Geographic Mosaic of Coevolution
  - Curr Biol 19(17):R735-R736 (2009)
  Natural selection can favor the coexistence of sexual and asexual forms of a species even within a single ecosystem, when hotspots of coevolution between hosts and parasites occur next to coldspots.
• Human Genetics: Measuring the Raw Material of Evolution
  - Curr Biol 19(17):R736-R738 (2009)
  By direct sequencing of two Y chromosomes inherited from the same paternal ancestor, a landmark study has derived a good direct estimate for the rate of base substitution mutations on the human Y chromosome.
• Evolution: No-Male's Land for an Amazonian Ant
  - Curr Biol 19(17):R738-R740 (2009)
  Recent work has shown that, in the Amazonian fungus-growing ant Mycocepurus smithii, queens use exclusively asexual reproduction and the male sex seems to have disappeared from the species. This finding illustrates the remarkable diversity of reproductive systems in ants.
• Protein Evolution: Innovative Chaps
  - Curr Biol 19(17):R740-R742 (2009)
  Mutations in proteins allow functional innovation, but can be critically destabilizing. Recent work shows how chaperonins can rescue innovative mutants, with implications for protein engineering and adaptive evolution.
• Form, force and flamboyance
  - Curr Biol 19(17):R743-R745 (2009)
  
• The mechanical cell
  - Curr Biol 19(17):R745-R748 (2009)
  
• Force and Length in the Mitotic Spindle
  - Curr Biol 19(17):R749-R761 (2009)
  The mitotic spindle assembles to a steady-state length at metaphase through the integrated action of molecular mechanisms that generate and respond to mechanical forces. While molecular mechanisms that produce force have been described, our understanding of how they integrate with each other, and with the assembly/disassembly mechanisms that regulate length, is poor. We review current understanding of the basic architecture and dynamics of the metaphase spindle, and some of the elementary force-producing mechanisms. We then discuss models for force integration and spindle length determination. We also emphasize key missing data that notably include absolute values of forces and how they vary as a function of position within the spindle.
• The Shape of Motile Cells
  - Curr Biol 19(17):R762-R771 (2009)
  Motile cells — fan-like keratocytes, hand-shaped nerve growth cones, polygonal fibroblasts, to name but a few — come in different shapes and sizes. We discuss the origins of this diversity as well as what shape tells us about the physics and biochemistry underlying cell movement. We start with geometric rules describing cell-edge kinetics that govern cell shape, followed by a discussion of the underlying biophysics; we consider actin treadmilling, actin–myosin contraction, cell-membrane deformations, adhesion, and the complex interactions between these modules, as well as their regulation by microtubules and Rho GTPases. Focusing on several different cell types, including keratocytes and fibroblasts, we discuss how dynamic cell morphology emerges from the interplay between the different motility modules and the environment.
• Domain-Driven Morphogenesis of Cellular Membranes
  - Curr Biol 19(17):R772-R780 (2009)
  Cellular membrane systems delimit and organize the intracellular space. Most of the morphological rearrangements in cells involve the coordinated remodeling of the lipid bilayer, the core of the membranes. This process is generally thought to be initiated and coordinated by specialized protein machineries. Nevertheless, it has become increasingly evident that the most essential part of the geometric information and energy required for membrane remodeling is supplied via the cooperative and synergistic action of proteins and lipids, as cellular shapes are constructed using the intrinsic dynamics, plasticity and self-organizing capabilities provided by the lipid bilayer. Here, we analyze the essential role of proteo-lipid membrane domains in conducting and coordinating morphological remodeling in cells.
• Conformational Changes and Signaling in Cell and Matrix Physics
  - Curr Biol 19(17):R781-R789 (2009)
  Physical factors drive evolution and play important roles in motility and attachment as well as in differentiation. As animal cells adhere to survive, they generate force and 'feel' various mechanical features of their surroundings, with mechanosensory mechanisms based in part on force-induced conformational changes. Single-molecule methods for in vitro nano-manipulation, together with new in situ proteomic approaches that exploit mass spectrometry, are helping to identify and characterize the molecules and mechanics of structural transitions within cells and matrices. Given the diversity of cell and molecular responses, networks of biomolecules with conformations and interactions sculpted by force seem more likely than singular mechanosensors. Elaboration of the proteins that unfold and change structure in the extracellular matrix and in cells is needed — particularly with regard to the force-driven kinetics — in order to understand the systems biology of sign! aling in development, differentiation, and disease.
• Biology and Physics of Cell Shape Changes in Development
  - Curr Biol 19(17):R790-R799 (2009)
  Together with cell growth, division and death, changes in cell shape are of central importance for tissue morphogenesis during development. Cell shape is the product of a cell's material and active properties balanced by external forces. Control of cell shape, therefore, relies on both tight regulation of intracellular mechanics and the cell's physical interaction with its environment. In this review, we first discuss the biological and physical mechanisms of cell shape control. We next examine a number of developmental processes in which cell shape change — either individually or in a coordinated manner — drives embryonic morphogenesis and discuss how cell shape is controlled in these processes. Finally, we emphasize that cell shape control during tissue morphogenesis can only be fully understood by using a combination of cellular, molecular, developmental and biophysical approaches.
• Dynamic Coordination of Cytoskeletal and Cell Wall Systems during Plant Cell Morphogenesis
  - Curr Biol 19(17):R800-R811 (2009)
  Underlying the architectural complexity of plants are diverse cell types that, under the microscope, easily reveal relationships between cell structure and specialized functions. Much less obvious are the mechanisms by which the cellular growth machinery and mechanical properties of the cell interact to dictate cell shape. The recent combined use of mutants, genomic analyses, sophisticated spectroscopies, and live cell imaging is providing new insight into how cytoskeletal systems and cell wall biosynthetic activities are integrated during morphogenesis. The purpose of this review is to discuss the unique geometric properties and physical processes that regulate plant cell expansion, then to overlay on this mechanical system some of the recent discoveries about the protein machines and cellular polymers that regulate cell shape. In the end, we hope to make clear that there are many interesting opportunities to develop testable mathematical models that improve our under! standing of how subcellular structures, protein motors, and extracellular polymers can exert effects at spatial scales that span cells, tissues, and organs.
• Sculpting the Bacterial Cell
  - Curr Biol 19(17):R812-R822 (2009)
  Prokaryotes come in a wide variety of shapes, determined largely by natural selection, physical constraints, and patterns of cell growth and division. Because of their relative simplicity, bacterial cells are excellent models for how genes and proteins can directly determine morphology. Recent advances in cytological methods for bacteria have shown that distinct cytoskeletal filaments composed of actin and tubulin homologs are important for guiding growth patterns of the cell wall in bacteria, and that the glycan strands that constitute the wall are generally perpendicular to the direction of growth. This cytoskeleton-directed cell wall patterning is strikingly reminiscent of how plant cell wall growth is regulated by microtubules. In rod-shaped bacilli, helical cables of actin-like MreB protein stretch along the cell length and orchestrate elongation of the cell wall, whereas the tubulin-like FtsZ protein directs formation of the division septum and the resulting cell! poles. The overlap and interplay between these two systems and the peptidoglycan-synthesizing enzymes they recruit are the major driving forces of cylindrical shapes. Round cocci, on the other hand, have lost their MreB cables and instead must grow mainly via their division septum, giving them their characteristic round or ovoid shapes. Other bacteria that lack MreB homologs or even cell walls use distinct cytoskeletal systems to maintain their distinct shapes. Here I review what is known about the mechanisms that determine the shape of prokaryotic cells.
• Cell Shape and Cell Division in Fission Yeast
  - Curr Biol 19(17):R823-R827 (2009)
  The fission yeast Schizosaccharomyces pombe has served as an important model organism for investigating cellular morphogenesis. This unicellular rod-shaped fission yeast grows by tip extension and divides by medial fission. In particular, microtubules appear to define sites of polarized cell growth by delivering cell polarity factors to the cell tips. Microtubules also position the cell nucleus at the cell middle, marking sites of cell division. Here, we review the microtubule-dependent mechanisms that regulate cell shape and cell division in fission yeast.
• Mechanosensing through Cooperative Interactions between Myosin II and the Actin Crosslinker Cortexillin I
  - Curr Biol 19(17):1421-1428 (2009)
  Background Mechanosensing governs many processes from molecular to organismal levels, including during cytokinesis where it ensures successful and symmetrical cell division. Although many proteins are now known to be force sensitive, myosin motors with their ATPase activity and force-sensitive mechanical steps are well poised to facilitate cellular mechanosensing. For a myosin motor to experience tension, the actin filament must also be anchored. Results Here, we find a cooperative relationship between myosin II and the actin crosslinker cortexillin I where both proteins are essential for cellular mechanosensory responses. Although many functions of cortexillin I and myosin II are dispensable for cytokinesis, all are required for full mechanosensing. Our analysis demonstrates that this mechanosensor has three critical elements: the myosin motor where the lever arm acts as a force amplifier, a force-sensitive bipolar thick-filament assembly, and a long-lived actin crosslinker, which anchors the actin filament so that the motor may experience tension. We also demonstrate that a Rac small GTPase inhibits this mechanosensory module during interphase, allowing the module to be primarily active during cytokinesis. Conclusions Overall, myosin II and cortexillin I define a cellular-scale mechanosensor that controls cell shape during cytokinesis. This system is exquisitely tuned through the enzymatic properties of the myosin motor, its lever arm length, and bipolar thick-filament assembly dynamics. The system also requires cortexillin I to stably anchor the actin filament so that the myosin motor can experience tension. Through this cross-talk, myosin II and cortexillin I define a cellular-scale mechanosensor that monitors and corrects shape defects, ensuring symmetrical cell division.
• Drosophila Cip4/Toca-1 Integrates Membrane Trafficking and Actin Dynamics through WASP and SCAR/WAVE
  - Curr Biol 19(17):1429-1437 (2009)
  Background Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes. Results Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing. Conclusion Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.
• The Geographic Mosaic of Sex and the Red Queen
  King KC Delph LF Jokela J Lively CM - Curr Biol 19(17):1438-1441 (2009)
  The maintenance of sexual reproduction in natural populations is a pressing question for evolutionary biologists [1] and [2]. Under the "Red Queen" hypothesis, coevolving parasites reduce the reproductive advantage of asexual reproduction by adapting to infect clonal genotypes after they become locally common [3], [4], [5] and [6]. In addition, the "geographic mosaic" theory of coevolution proposes that structured populations of interacting species can produce selection mosaics manifested as coevolutionary "hot spots" and "cold spots" [7]. Here, we tested whether a steep, habitat-specific cline in the frequency of sexual reproduction in a freshwater snail could be explained by the existence of hot spots and cold spots for coevolving parasites. We found that the shallow-water margins of lakes, where sexual reproduction is most common, are coevolutionary hot spots, and that deeper habitats are cold spots. These results are consistent with the geographic m! osaic theory, in that the intensity of selection resulting from biological interactions can vary sharply in space. The results also support the Red Queen hypothesis, in that sex is associated with coevolutionary hot spots for virulent parasites.
• Evolutionary Response to Sexual Selection in Male Genital Morphology
  - Curr Biol 19(17):1442-1446 (2009)
  Male genital morphology is characterized by two striking and general patterns of morphological variation: rapid evolutionary divergence in shape and complexity, and relatively low scaling relationships with body size. These patterns of variation have been ascribed to the action of sexual selection [1] and [2]. Among species, monogamous taxa tend to have relatively less complex male genital morphology than do polygamous taxa [3]. However, although variation in male genital morphology can be associated with variation in mating [4] and [5] and fertilization success [6], [7], [8], [9] and [10], there is no direct evidence that sexual selection generates the evolutionary changes in male genital shape that underlie observed macroevolutionary patterns. Moreover, the hypothesis that sexual selection acts to reduce the scaling relationship between body and genital size is based entirely on the theoretical argument that male genitalia should be selected to provide an appropriate! mechanical and/or stimulatory fit to the most commonly encountered female genitalia [2] and [11]. Here, using the dung beetle Onthophagus taurus, we combine the power of experimental evolution with multivariate selection and quantitative genetic analyses to provide the most comprehensive evidence available of the form and evolutionary consequences of sexual selection acting on male genital morphology.
• Ecdysone Receptor Acts in fruitless- Expressing Neurons to Mediate Drosophila Courtship Behaviors
  - Curr Biol 19(17):1447-1452 (2009)
  In Drosophila melanogaster, fruitless (fru) encodes male-specific transcription factors (FRUM; encoded by fru P1) required for courtship behaviors (reviewed in [1]). However, downstream effectors of FRUM throughout development are largely unknown [2], [3], [4] and [5]. During metamorphosis the nervous system is remodeled for adult function, the timing of which is coordinated by the steroid hormone 20-hydroxyecdysone (ecdysone) through the ecdysone receptor, a heterodimer of the nuclear receptors EcR (isoforms are EcR-A, EcR-B1, or EcR-B2) and Ultraspiracle (USP) (reviewed in [6]). Here, we show that genes identified as regulated downstream of FRUM during metamorphosis are significantly overrepresented with genes known to be regulated in response to ecdysone or EcR. FRUM and EcR isoforms are coexpressed in neurons in the CNS during metamorphosis in an isoform-specific manner. Reduction of EcR-A levels in fru P1-expressing neurons of males caused a significant increase i! n male-male courtship activity and significant reduction in size of two antennal lobe glomeruli. Additional genes were identified that are regulated downstream of EcR-A in fru P1-expressing neurons. Thus, EcR-A is required in fru P1-expressing neurons for wild-type male courtship behaviors and the establishment of male-specific neuronal architecture.
• Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree
  Xue Y Wang Q Long Q Ng BL Swerdlow H Burton J Skuce C Taylor R Abdellah Z Zhao Y Asan Macarthur DG Quail MA Carter NP Yang H Tyler-Smith C - Curr Biol 19(17):1453-1457 (2009)
  Understanding the key process of human mutation is important for many aspects of medical genetics and human evolution. In the past, estimates of mutation rates have generally been inferred from phenotypic observations or comparisons of homologous sequences among closely related species [1], [2] and [3]. Here, we apply new sequencing technology to measure directly one mutation rate, that of base substitutions on the human Y chromosome. The Y chromosomes of two individuals separated by 13 generations were flow sorted and sequenced by Illumina (Solexa) paired-end sequencing to an average depth of 11× or 20×, respectively [4]. Candidate mutations were further examined by capillary sequencing in cell-line and blood DNA from the donors and additional family members. Twelve mutations were confirmed in 10.15 Mb; eight of these had occurred in vitro and four in vivo. The latter could be placed in different positions on the pedigree and led to a mutation-rate measurement of 3.! 0 × 10−8 mutations/nucleotide/generation (95% CI: 8.9 × 10−9–7.0 × 10−8), consistent with estimates of 2.3 × 10−8–6.3 × 10−8 mutations/nucleotide/generation for the same Y-chromosomal region from published human-chimpanzee comparisons [5] depending on the generation and split times assumed.
• Dissociation of Neural Mechanisms Underlying Orientation Processing in Humans
  - Curr Biol 19(17):1458-1462 (2009)
  Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and the discovery of that property has dramatically shaped how we conceptualize visual processing [1], [2], [3], [4], [5] and [6]. However, much remains unknown about the neural substrates of this basic building block of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS), which can significantly attenuate neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7] and [8]. Using rTMS to suppress neural responses evoked by stimuli falling within a local region of the visual field, we were able to dissociate two distinct components of the neural circuitry underlying orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking ! was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened after rTMS. This dissociation implies that orientation processing in humans relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is governed by patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses amongst those cortical neurons.
• Deubiquitinase Activities Required for Hepatocyte Growth Factor-Induced Scattering of Epithelial Cells
  - Curr Biol 19(17):1463-1466 (2009)
  The scattering response of epithelial cells to activation of the Met receptor tyrosine kinase represents one facet of an "invasive growth" program [1] and [2]. It is a complex event that incorporates loss of cell-cell adhesion, morphological changes, and cell motility. Ubiquitination is a reversible posttranslational modification that may target proteins for degradation or coordinate signal transduction pathways [3] and [4]. There are 79 active deubiquitinating enzymes (DUBs) predicted in the human genome [5] and [6]. Here, via a small interfering RNA (siRNA) library approach, we have identified 12 DUBs that are necessary for aspects of the hepatocyte growth factor (HGF)-dependent scattering response of A549 cells. Different phenotypes are evident that range from full loss of scattering, similar to receptor knockdown (e.g., USP30, USP33, USP47), to loss of cell-cell contacts even in the absence of HGF but defective motility (e.g., USP3, ATXN3L). The knockdowns do n! ot incur defective receptor, phosphatidylinositol 3-kinase, or MAP kinase activation. Our data suggest widespread involvement of the ubiquitin system at multiple stages of the Met activation response, implying significant crosstalk with phosphorylation-based transduction pathways. Development of small-molecule inhibitors of particular DUBs may offer a therapeutic approach to contain metastasis.
• Ska3 Is Required for Spindle Checkpoint Silencing and the Maintenance of Chromosome Cohesion in Mitosis
  - Curr Biol 19(17):1467-1472 (2009)
  The mitotic spindle checkpoint monitors proper bipolar attachment of chromosomes to the mitotic spindle [1]. Previously, depletion of the novel kinetochore complex Ska1/Ska2 was found to induce a metaphase delay [2]. By using bioinformatics, we identified C13orf3, predicted to associate with kinetochores. Recently, three laboratories independently indentified C13orf3 as an additional Ska complex component, and therefore we adopted the name Ska3 [3], [4] and [5]. We found that cells depleted of Ska3 by RNAi achieve metaphase alignment but fail to silence the spindle checkpoint or enter anaphase. After hours of metaphase arrest, chromatids separate but retain robust kinetochore-microtubule attachments. Ska3-depleted cells accumulate high levels of the checkpoint protein Bub1 at kinetochores. Ska3 protein accumulation at kinetochores in prometaphase is dependent on Sgo1 protein. Sgo1, which accumulates at the centromeres earlier, in prophase, is not dependent on Ska3. Sgo! 1-depleted cells show a stronger premature chromatid separation phenotype than those depleted of Ska3. We hypothesize that Ska3 functions to coordinate checkpoint signaling from the microtubule binding sites within a kinetochore by laterally linking the individual binding sites. We suggest that this network plays a major role in silencing the spindle checkpoint when chromosomes are aligned at metaphase to allow timely anaphase onset and mitotic exit.
• A Blood-Borne PDGF/VEGF-like Ligand Initiates Wound-Induced Epidermal Cell Migration in Drosophila Larvae
  - Curr Biol 19(17):1473-1477 (2009)
  Epidermal cell migration is critical for restoration of tissue structure and function after damage [1]. However, the mechanisms by which differentiated cells neighboring the wound sense the wound and assume a motile phenotype remain unclear. Here, we show that Pvr, a receptor tyrosine kinase (RTK) related to platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, and one of its ligands, Pvf1, are required for epidermal wound closure. Morphological comparison of wound-edge cells lacking Pvr or the Jun N-terminal kinase (JNK) signaling pathway previously implicated in larval wound closure [2] suggests that Pvr signaling leads wound-margin epidermal cells to extend actin-based cell processes into the wound gap while JNK mediates transient dedifferentiation of cells at the wound margin. Genetic epistasis experiments reinforce the conclusion that the JNK and Pvr signaling pathways act in parallel. Tissue-specific knockdown and rescue e! xperiments suggest that epidermally derived Pvf1 may be sequestered in the blood and that tissue damage exposes blood-borne Pvf1 to Pvr receptors on wound-edge epidermal cells and initiates the extension of cell processes into the wound gap. These results uncover a novel mechanism of sensing tissue damage and suggest that PDGF/VEGF ligands and receptors may play a conserved autocrine role in epidermal wound closure.
• Key Features of the X Inactivation Process Are Conserved between Marsupials and Eutherians
  - Curr Biol 19(17):1478-1484 (2009)
  In female marsupials, X chromosome inactivation (XCI) is imprinted, affecting the paternal X chromosome. One model, supported by recent studies [1] and [2], proposes that XCI in marsupials is achieved through inheritance of an already silent X chromosome from the father [3], [4], [5] and [6], with XCI initiated by meiotic sex chromosome inactivation (MSCI) [7] and [8]. This model is appealing because marsupials have no Xist gene [9], [10], [11] and [12] and the marsupial inactive X chromosome is epigenetically dissimilar to that of mice, apparently lacking repressive histone marks such as H3K27 trimethylation [13]. A central prediction of the meiotic inactivation model of XCI is that silencing of genes on the X chromosome, initiated during male meiosis, is stably maintained during subsequent spermiogenesis. Here we characterize XCI in the male germline and female soma of the marsupial Monodelphis domestica. Contrary to the meiotic inactivation model, we find that X gen! es silenced by MSCI are reactivated after meiosis and are subsequently inactivated in the female. A reexamination of the female somatic inactive marsupial X chromosome reveals that it does share common properties with that of eutherians, including H3K27 trimethylation and targeting to the perinucleolar compartment. We conclude that aspects of the XCI process are more highly conserved in therian mammals than previously thought.
• Repression of Apical Homeobox Genes Is Required for Embryonic Root Development in Arabidopsis
  - Curr Biol 19(17):1485-1490 (2009)
  Development of seed plant embryos is polarized along the apical-basal axis. This polarization occurs in the absence of cell migration and culminates in the establishment of two distinct pluripotent cell populations: the shoot apical meristem (SAM) and root meristem (RM), which postembryonically give rise to the entire shoot and root systems of the plant. The acquisition of genetic pathways that delimit root from shoot during embryogenesis must have played a pivotal role during land plant evolution because roots evolved after shoots in ancestral vascular plants and may be shoot-derived organs [1]. However, such pathways are very poorly understood. Here we show that RM establishment in the model plant Arabidopsis thaliana requires apical confinement of the Class III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) proteins PHABULOSA (PHB) and PHAVOLUTA (PHV), which direct both SAM development and shoot lateral organ polarity [2] and [3]. Failure to restrict PHB and PHV expression! apically via a microRNA-dependent pathway prevents correct elaboration of the embryonic root development program and results in embryo lethality. As such, repression of a fundamental shoot development pathway is essential for correct root development. Additionally, our data suggest that a single patterning process, based on HD-ZIP III repression, mediates both apical-basal and radial polarity in the embryo and lateral organ polarity in the shoot.
• The Bacterial ZapA-like Protein ZED Is Required for Mitochondrial Division
  - Curr Biol 19(17):1491-1497 (2009)
  Bacterial cell division systems that include FtsZ are found throughout prokaryotes [1]. Mitochondria arose from an endosymbiotic α-proteobacterial ancestor and proliferate by division [2], [3] and [4]. However, how the mitochondrial division system was established from bacterial division is not clear. Here, we have isolated intact mitochondrial division (MD) machineries from the primitive red alga Cyanidioschyzon merolae and identified a bacterial ZapA-like protein, ZED, that constricts the basal structure of MD machinery with FtsZ. ZED contains a predicted mitochondrial transit signal and two coiled-coil regions and has partial homology with the bacterial division protein ZapA [5]. Cytological studies revealed that ZED accumulates to form a ring structure that colocalizes with FtsZ beneath the inner membrane. ZED proteins are expressed just before mitochondrial division. The short-form ZED (S-ZED) then appears at the mitochondrial constriction phase. Protein-protein ! interaction analysis and transient expression of antisense against ZED showed that S-ZED interacts with FtsZ1 to constitute the basal structure of the MD machinery and is required for mitochondrial division. We also demonstrate compelling functional similarity between bacterial ZapA and mitochondrial ZED, suggesting that the bacterial cell division system was incorporated into the MD machinery with remodeling of bacterial division proteins during evolution.
• Centriole Age Underlies Asynchronous Primary Cilium Growth in Mammalian Cells
  - Curr Biol 19(17):1498-1502 (2009)
  Primary cilia are microtubule-based sensory organelles that play important roles in development and disease [1]. They are required for Sonic hedgehog (Shh) [2], [3] and [4] and platelet-derived growth factor (PDGF) [5] signaling. Primary cilia grow from the older of the two centrioles of the centrosome, referred to as the mother centriole. In cycling cells, the cilium typically grows in G1 and is lost before mitosis, but the regulation of its growth is poorly understood. Centriole duplication at G1/S results in two centrosomes, one with an older mother centriole and one with a new mother centriole, that are segregated in mitosis. Here we report that primary cilia grow asynchronously in sister cells resulting from a mitotic division and that the sister cell receiving the older mother centriole usually grows a primary cilium first. We also show that the signaling proteins inversin [6] and PDGFRα localize asynchronously to sister cell primary cilia and that sister cells ! respond asymmetrically to Shh. These results suggest that the segregation of differently aged mother centrioles, an asymmetry inherent to every animal cell division, can influence the ability of sister cells to respond to environmental signals, potentially altering the behavior or fate of one or both sister cells.