Tissue flow regulates planar cell polarity independently of the Frizzled core pathway.

Planar cell polarity (PCP) regulates the orientation of external structures. A core group of proteins that includes Frizzled forms the heart of the PCP regulatory system. Other PCP mechanisms that are independent of the core group likely exist, but their underlying mechanisms are elusive. Here, we show that tissue flow is a mechanism governing core group-independent PCP on the Drosophila notum. Loss of core group function only slightly affects bristle orientation in the adult central notum. This near-normal PCP results from tissue flow-mediated rescue of random bristle orientation during the pupal stage. Manipulation studies suggest that tissue flow can orient bristles in the opposite direction to the flow. This process is independent of the core group and implies that the apical extracellular matrix functions like a "comb" to align bristles. Our results reveal the significance of cooperation between tissue dynamics and extracellular substances in PCP establishment.

Tiling mechanisms of the Drosophila compound eye through geometrical tessellation.

Tiling patterns are observed in many biological structures. The compound eye is an interesting example of tiling and is often constructed by hexagonal arrays of ommatidia, the optical unit of the compound eye. Hexagonal tiling may be common due to mechanical restrictions such as structural robustness, minimal boundary length, and space-filling efficiency. However, some insects exhibit tetragonal facets.1-4 Some aquatic crustaceans, such as shrimp and lobsters, have evolved with tetragonal facets.5-8 Mantis shrimp is an insightful example as its compound eye has a tetragonal midband region sandwiched between hexagonal hemispheres.9,10 This casts doubt on the naive explanation that hexagonal tiles recur in nature because of their mechanical stability. Similarly, tetragonal tiling patterns are also observed in some Drosophila small-eye mutants, whereas the wild-type eyes are hexagonal, suggesting that the ommatidial tiling is not simply explained by such mechanical restrictions. If so, how are the hexagonal and tetragonal patterns controlled during development? Here, we demonstrate that geometrical tessellation determines the ommatidial tiling patterns. In small-eye mutants, the hexagonal pattern is transformed into a tetragonal pattern as the relative positions of neighboring ommatidia are stretched along the dorsal-ventral axis. We propose that the regular distribution of ommatidia and their uniform growth collectively play an essential role in the establishment of tetragonal and hexagonal tiling patterns in compound eyes.

Collective nuclear behavior shapes bilateral nuclear symmetry for subsequent left-right asymmetric morphogenesis in Drosophila.

Proper organ development often requires nuclei to move to a specific position within the cell. To determine how nuclear positioning affects left-right (LR) development in the Drosophila anterior midgut (AMG), we developed a surface-modeling method to measure and describe nuclear behavior at stages 13-14, captured in three-dimensional time-lapse movies. We describe the distinctive positioning and a novel collective nuclear behavior by which nuclei align LR symmetrically along the anterior-posterior axis in the visceral muscles that overlie the midgut and are responsible for the LR-asymmetric development of this organ. Wnt4 signaling is crucial for the collective behavior and proper positioning of the nuclei, as are myosin II and the LINC complex, without which the nuclei fail to align LR symmetrically. The LR-symmetric positioning of the nuclei is important for the subsequent LR-asymmetric development of the AMG. We propose that the bilaterally symmetrical positioning of these nuclei may be mechanically coupled with subsequent LR-asymmetric morphogenesis.

Weakening of resistance force by cell-ECM interactions regulate cell migration directionality and pattern formation.

Collective migration of epithelial cells is a fundamental process in multicellular pattern formation. As they expand their territory, cells are exposed to various physical forces generated by cell-cell interactions and the surrounding microenvironment. While the physical stress applied by neighbouring cells has been well studied, little is known about how the niches that surround cells are spatio-temporally remodelled to regulate collective cell migration and pattern formation. Here, we analysed how the spatio-temporally remodelled extracellular matrix (ECM) alters the resistance force exerted on cells so that the cells can expand their territory. Multiple microfabrication techniques, optical tweezers, as well as mathematical models were employed to prove the simultaneous construction and breakage of ECM during cellular movement, and to show that this modification of the surrounding environment can guide cellular movement. Furthermore, by artificially remodelling the microenvironment, we showed that the directionality of collective cell migration, as well as the three-dimensional branch pattern formation of lung epithelial cells, can be controlled. Our results thus confirm that active remodelling of cellular microenvironment modulates the physical forces exerted on cells by the ECM, which contributes to the directionality of collective cell migration and consequently, pattern formation.

Osmotic gradients induce stable dome morphogenesis on extracellular matrix.

One of the fundamental processes in morphogenesis is dome formation, but many of the mechanisms involved are unexplored. Previous in vitro studies showed that an osmotic gradient is the driving factor of dome formation. However, these investigations were performed without extracellular matrix (ECM), which provides structural support to morphogenesis. With the use of ECM, we observed that basal hypertonic stress induced stable domes in vitro that have not been seen in previous studies. These domes developed as a result of ECM swelling via aquaporin water transport activity. Based on computer simulation, uneven swelling, with a positive feedback between cell stretching and enhanced water transport, was a cause of dome formation. These results indicate that osmotic gradients induce dome morphogenesis via both enhanced water transport activity and subsequent ECM swelling.

Complex furrows in a 2D epithelial sheet code the 3D structure of a beetle horn.

The external organs of holometabolous insects are generated through two consecutive processes: the development of imaginal primordia and their subsequent transformation into the adult structures. During the latter process, many different phenomena at the cellular level (e.g. cell shape changes, cell migration, folding and unfolding of epithelial sheets) contribute to the drastic changes observed in size and shape. Because of this complexity, the logic behind the formation of the 3D structure of adult external organs remains largely unknown. In this report, we investigated the metamorphosis of the horn in the Japanese rhinoceros beetle Trypoxylus dichotomus. The horn primordia is essentially a 2D epithelial cell sheet with dense furrows. We experimentally unfolded these furrows using three different methods and found that the furrow pattern solely determines the 3D horn structure, indicating that horn formation in beetles occurs by two distinct processes: formation of the furrows and subsequently unfolding them. We postulate that this developmental simplicity offers an inherent advantage to understanding the principles that guide 3D morphogenesis in insects.

Mathematical model of collective cell migrations based on cell polarity.

Individual cells migrate toward the direction of the cell polarity generated by interior or exterior factors. Under situations without guides such as chemoattractants, they migrate randomly. On the other hand, it has been observed that cell groups lead to systematic collective cell migrations. For example, Dictyostelium discoideum and Madin-Darby canine kidney (epithelial) cells exhibit typical collective cell migration patterns such as uniformly directional migration and rotational migration. In particular, it has been suggested from experimental investigations that rotational migrations are intimately related to morphogenesis of organs and tissues in several species. Thus, it is conjectured that collective cell migrations are controlled by universal mechanisms of cells. In this paper, we review actual experimental data related to collective cell migrations on dishes and show that our self-propelled particle model based on the cell polarity can accurately represent actual migration behaviors. Furthermore, we show that collective cell migration modes observed in our model are robust.

Theta-alpha EEG phase distributions in the frontal area for dissociation of visual and auditory working memory.

Working memory (WM) is known to be associated with synchronization of the theta and alpha bands observed in electroencephalograms (EEGs). Although frontal-posterior global theta synchronization appears in modality-specific WM, local theta synchronization in frontal regions has been found in modality-independent WM. How frontal theta oscillations separately synchronize with task-relevant sensory brain areas remains an open question. Here, we focused on theta-alpha phase relationships in frontal areas using EEG, and then verified their functional roles with mathematical models. EEG data showed that the relationship between theta (6 Hz) and alpha (12 Hz) phases in the frontal areas was about 1:2 during both auditory and visual WM, and that the phase distributions between auditory and visual WM were different. Next, we used the differences in phase distributions to construct FitzHugh-Nagumo type mathematical models. The results replicated the modality-specific branching by orthogonally of the trigonometric functions for theta and alpha oscillations. Furthermore, mathematical and experimental results were consistent with regards to the phase relationships and amplitudes observed in frontal and sensory areas. These results indicate the important role that different phase distributions of theta and alpha oscillations have in modality-specific dissociation in the brain.

A ciliate memorizes the geometry of a swimming arena.

Previous studies on adaptive behaviour in single-celled organisms have given hints to the origin of their memorizing capacity. Here we report evidence that a protozoan ciliate Tetrahymena has the capacity to learn the shape and size of its swimming space. Cells confined in a small water droplet for a short period were found to recapitulate circular swimming trajectories upon release. The diameter of the circular trajectories and their duration reflected the size of the droplet and the period of confinement. We suggest a possible mechanism for this adaptive behaviour based on a Ca(2+) channel. In our model, repeated collisions with the walls of a confining droplet result in a slow rise in intracellular calcium that leads to a long-term increase in the reversal frequency of the ciliary beat.

Dachsous-dependent asymmetric localization of spiny-legs determines planar cell polarity orientation in Drosophila.

In Drosophila, planar cell polarity (PCP) molecules such as Dachsous (Ds) may function as global directional cues directing the asymmetrical localization of PCP core proteins such as Frizzled (Fz). However, the relationship between Ds asymmetry and Fz localization in the eye is opposite to that in the wing, thereby causing controversy regarding how these two systems are connected. Here, we show that this relationship is determined by the ratio of two Prickle (Pk) isoforms, Pk and Spiny-legs (Sple). Pk and Sple form different complexes with distinct subcellular localizations. When the amount of Sple is increased in the wing, Sple induces a reversal of PCP using the Ds-Ft system. A mathematical model demonstrates that Sple is the key regulator connecting Ds and the core proteins. Our model explains the previously noted discrepancies in terms of the differing relative amounts of Sple in the eye and wing.

Radiation measurements in the Chiba Metropolitan Area and radiological aspects of fallout from the Fukushima Dai-ichi Nuclear Power Plants accident.

Large amounts of radioactive substances were released into the environment from the Fukushima Dai-ichi Nuclear Power Plants in eastern Japan as a consequence of the great earthquake (M 9.0) and tsunami of 11 March 2011. Radioactive substances discharged into the atmosphere first reached the Chiba Metropolitan Area on 15 March. We collected daily samples of air, fallout deposition, and tap water starting directly after the incident and measured their radioactivity. During the first two months maximum daily concentrations of airborne radionuclides observed at the Japan Chemical Analysis Center in the Chiba Metropolitan Area were as follows: 4.7 × 10(1) Bq m(-3) of (131)I, 7.5 Bq m(-3) of (137)Cs, and 6.1 Bq m(-3) of (134)Cs. The ratio of gaseous iodine to total iodine ranged from 5.2 × 10(-1) to 7.1 × 10(-1). Observed deposition rate maxima were as follows: 1.7 × 10(4) Bq m(-2) d(-1) of (131)I, 2.9 × 10(3) Bq m(-2) d(-1) of (137)Cs, and 2.9 × 10(3) Bq m(-2) d(-1) of (134)Cs. The deposition velocities (ratio of deposition rate to concentration) of cesium radionuclides and (131)I were detectably different. Radioactivity in tap water caused by the accident was detected several days after detection of radioactivity in fallout in the area. Radiation doses were estimated from external radiation and internal radiation by inhalation and ingestion of tap water for people living outdoor in the Chiba Metropolitan Area following the Fukushima accident.

A mathematical model of cleavage.

In the present paper, we propose a mathematical model of cleavage. Cleavage is a process during the early stages of development in which the fertile egg undergoes repeated division keeping the cluster size almost constant. During the cleavage process individual cells repeat cell division in an orderly manner to form a blastula, however, the mechanism which achieves such a coordination is still not very clear. In the present research, we took sea urchin as an example and focused on the diffusion of chemical substances from the animal and vegetal pole. By considering chemotactic motion of the centrosomes, we constructed a mathematical model that describes the processes in the early stages of cleavage.