Oriented Cell Division

BACKGROUND: Endothelial cell (EC) generation and turnover by self-proliferation contributes to vascular repair and regeneration. The ability to accurately measure the dynamics of EC generation would advance our understanding of cellular mechanisms of vascular homeostasis and diseases. However, it is currently challenging to evaluate the dynamics of EC generation in large vessels such as arteries because of their infrequent proliferation. METHODS: By using dual recombination systems based on Cre-loxP and Dre-rox, we developed a genetic system for temporally seamless recording of EC proliferation in vivo...

INTRODUCTION: Sensory processing is profoundly regulated by brain neuromodulatory systems. One of the main neuromodulators is serotonin which influences higher cognitive functions, such as different aspects of perceptual processing. Accordingly, malfunction in the serotonergic system may lead to visual illusion in psychiatric disorders, such as autism and schizophrenia. This study aims to investigate the serotonergic modulation of visual responses of neurons to stimulus orientation in the primary visual cortex...

The nonmotile primary cilium is a sensory structure found on most mammalian cell types that integrates multiple signaling pathways involved in tissue development and postnatal function. As such, mutations disrupting cilia activities cause a group of disorders referred to as ciliopathies. These disorders exhibit a wide spectrum of phenotypes impacting nearly every tissue. In the kidney, primary cilia dysfunction caused by mutations in polycystin 1 (Pkd1), polycystin 2 (Pkd2), or polycystic kidney and hepatic disease 1 (Pkhd1), result in polycystic kidney disease (PKD), a progressive disorder causing renal functional decline and end-stage renal disease...

During the course of brain development, Radial Glial Progenitor (RGP) cells give rise to most of the neurons required for a functional cortex. RGPs can undergo symmetric divisions, which result in RGP duplication, or asymmetric divisions, which result in one RGP as well as one to four neurons. The control of this balance is not fully understood, but must be closely regulated to produce the cells required for a functioning cortex, and to maintain the stem cell pool. In this study, we show that the balance between symmetric and asymmetric RGP divisions is in part regulated by the actions of two kinesins, Kif1A and Kif13B, which we find have opposing roles in neurogenesis through their action on the mitotic spindle in dividing RGPs...

The algal ancestors of land plants underwent a transition from a unicellular to a multicellular body plan.1 This transition likely took place early in streptophyte evolution, sometime after the divergence of the Chlorokybophyceae/Mesostigmatophyceae lineage, but before the divergence of the Klebsormidiophyceae lineage.2 How this transition was brought about is unknown; however, it was likely facilitated by the evolution of novel mechanisms to spatially regulate morphogenesis. In land plants, RHO of plant (ROP) signaling plays a conserved role in regulating polarized cell growth and cell division orientation to orchestrate morphogenesis...

During development, cells are subject to stochastic fluctuations in their positions (i.e. cell-level noise) which can potentially, lead to morphological noise (i.e., stochastic differences between morphologies that are expected to be equal, like the right and left sides of bilateral organisms). In this study we explore new and already existing hypotheses on buffering mechanisms against cell-level noise. Many of these hypotheses focus on how the boundaries between territories of gene expression remain regular and well-defined in spite of cell-level noise and division...

During early development, cartilage provides shape and stability to the embryo while serving as a precursor for the skeleton. Correct formation of embryonic cartilage is hence essential for healthy development. In vertebrate cranial cartilage, it has been observed that a flat and laterally extended macroscopic geometry is linked to regular microscopic structure consisting of tightly packed, short, transversal clonar columns. However, it remains an ongoing challenge to identify how individual cells coordinate to successfully shape the tissue, and more precisely which mechanical interactions and cell behaviors contribute to the generation and maintenance of this columnar cartilage geometry during embryogenesis...

Epithelia are the first organized tissues that appear during development. In many animal embryos, early divisions give rise to a polarized monolayer, the primary epithelium, rather than a random aggregate of cells. Here, we review the mechanisms by which cells organize into primary epithelia in various developmental contexts. We discuss how cells acquire polarity while undergoing early divisions. We describe cases where oriented divisions constrain cell arrangement to monolayers including organization on top of yolk surfaces...

The cytoplasmic Ca2+ concentration and the activity of K+ channels on the plasma membrane regulate cellular processes ranging from mitosis to oriented migration. The interplay between Ca2+ and K+ signals is intricate, and different cell types rely on peculiar cellular mechanisms. Derangement of these mechanisms accompanies the neoplastic progression. The calcium signals modulated by voltage-gated (KV ) and calcium-dependent (KCa ) K+ channel activity regulate progression of the cell division cycle, the release of growth factors, apoptosis, cell motility and migration...

The correct assembly of the spindle apparatus directly regulates the precise separation of chromosomes in mouse oocytes, which is crucial for obtaining high-quality oocytes capable of successful fertilization. The localization, assembly, migration, and disassembly of the spindle are regulated by a series of spindle-associated proteins, which exhibit unique expression level variations and specific localization in oocytes. Proteomic analysis revealed that among many representative spindle-associated proteins, the expression level of nucleolar and spindle-associated protein 1 (NUSAP1) significantly increased after meiotic resumption, with a magnitude of change higher than that of other proteins...

Loss of cell polarity and disruption of tissue organization are key features of tumorigenesis that are intrinsically linked to spindle orientation. Epithelial tumors are often characterized by spindle orientation defects, but how these defects impact tumor formation driven by common oncogenic mutations is not fully understood. Here, we examine the role of spindle orientation in adult epidermis by deleting a key spindle regulator, LGN, in normal tissue and in a PTEN-deficient mouse model. We report that LGN deficiency in PTEN mutant epidermis leads to a 3-fold increase in the likelihood of developing tumors on the snout, and an over 10-fold increase in tumor burden...

UNLABELLED: Genomic information must be faithfully transmitted into two daughter cells during cell division. To ensure the transmission process, interphase chromatin is further condensed into mitotic chromosomes. Although protein factors like condensins and topoisomerase IIα are involved in the assembly of mitotic chromosomes, the physical bases of the condensation process remain unclear. Macromolecular crowding/depletion force, an effective attractive force that arises between large structures in crowded environments around chromosomes, may contribute to the condensation process...

BACKGROUND: Analyses of collective cell migration and orientation phenomena are needed to assess the behavior of multicellular clusters. While some tools to the authors' knowledge none is capable to analyze collective migration, cellular orientation and proliferation in phase contrast images simultaneously. METHODS: We provide a tool based to analyze phase contrast images of dense cell layers. PIV is used to calculatevelocity fields, while the structure tensor provides cellular orientation...

Correct chromosome segregation during cell division depends on proper connections between spindle microtubules and kinetochores. During prometaphase, kinetochores are temporarily covered with a dense protein meshwork known as the fibrous corona. Formed by oligomerization of ROD/ZW10/ZWILCH-SPINDLY (RZZ-S) complexes, the fibrous corona promotes spindle assembly, chromosome orientation, and spindle checkpoint signaling. The molecular requirements for formation of the fibrous corona are not fully understood. Here, we show that the fibrous corona depends on the mitotic kinesin CENP-E and that poorly expanded fibrous coronas after CENP-E depletion are functionally compromised...

Cancer cell proliferation is affected by post-translational modifications of tubulin. Especially, overexpression or depletion of enzymes for modifications on the tubulin C-terminal region perturbs dynamic instability of the spindle body. Those modifications include processing of C-terminal amino acids of α-tubulin; detyrosination, and a removal of penultimate glutamic acid (Δ2). We previously found a further removal of the third last glutamic acid, which generates so-called Δ3-tubulin...

During cell cycle progression in Saccharomyces cerevisiae, spindle pole bodies (SPBs) are duplicated during the G1/S-phase transition. SPBs are crucial for the organization of both the spindle and astral microtubules, and their orientation defines the direction of nuclear division. In this process, an old SPB, which serves as the template SPB during the duplication process, is oriented toward the bud side. The patterning microtubule plus-end tracking protein, Kar9, plays an important role in the orientation of SPBs by asymmetrically localizing to the old SPB...

INTRODUCTION: The repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery. AIMS: The present study aims to explore the potential of Simvastatin (SIM), a drug used in the treatment of high cholesterol, and thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant, antiinflammatory, anti-cancer, and activities like tissue growth and division, hormone regulation, immune response and development, and cell signaling...

BACKGROUND AND AIMS: Tropaeolaceae (Brassicales) comprise ca. 100 species native to South and Central America. Tropaeolaceae flowers have a nectar spur, formed by a late expansion and evagination of the fused proximal region of the perianth (i.e. the floral tube). This spur is formed in the domain of the tube oriented towards the inflorescence axis, which corresponds to the adaxial floral region. However, little is known about the molecular mechanisms responsible for the evolution of spurs in Tropaeolaceae...

BACKGROUND: Cardiac ventricles provide the contractile force of the beating heart throughout life. How the primitive endocardium-layered myocardial projections called trabeculae form and mature into the adult ventricles is of great interest for biology and regenerative medicine. Trabeculation is dependent on the signaling protein Nrg1 (neuregulin-1). However, the mechanism of action of Nrg1 and its role in ventricular wall maturation are poorly understood. METHODS: We investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development using confocal imaging, transcriptomics, and biochemical approaches in mice with cardiac-specific inactivation or overexpression of Nrg1...

Throughout mitosis, a plethora of processes must be efficiently concerted to ensure cell proliferation and tissue functionality. The mitotic spindle does not only mediate chromosome segregation, but also defines the axis of cellular division, thus determining tissue morphology. Functional spindle orientation relies on precise actin dynamics, shaped in mitosis by the LIMK1-Cofilin axis. The kinase Haspin acts as a guardian of faithful chromosome segregation that ensures amphitelic chromosome attachment and prevents unscheduled cohesin cleavage...