PubMed Health⌕ Search

Biomedical subjects

Shigeru Kondo

Publications and source records attributed to Shigeru Kondo.

12 recordsLinked to original sources

Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement.

Many animals have a variety of pigment patterns, even within a species, and these patterns may be one of the driving forces of speciation. Recent molecular genetic studies on zebrafish have revealed that interaction among pigment cells plays a key role in pattern formation, but the mechanism of pattern formation is unclear. The zebrafish jaguar/obelix mutant has broader stripes than wild-type fish. In this mutant, the development of pigment cells is normal but their distribution is altered, making these fish ideal for studying the process of pigment pattern formation. Here, we utilized a positional cloning method to determine that the inwardly rectifying potassium channel 7.1 (Kir7.1) gene is responsible for pigment cell distribution among jaguar/obelix mutant fish. Furthermore, in jaguar/obelix mutant alleles, we identified amino acid changes in the conserved region of Kir7.1, each of which affected K(+) channel activity as demonstrated by patch-clamp experiments. Injection of a bacterial artificial chromosome containing the wild-type Kir7.1 genomic sequence rescued the jaguar/obelix phenotype. From these results, we conclude that mutations in Kir7.1 are responsible for jaguar/obelix. We also determined that the ion channel function defect of melanophores expressing mutant Kir7.1 altered the cellular response to external signals. We discovered that mutant melanophores cannot respond correctly to the melanosome dispersion signal derived from the sympathetic neuron and that melanosome aggregation is constitutively activated. In zebrafish and medaka, it is well known that melanosome aggregation and subsequent melanophore death increase when fish are kept under constant light conditions. These observations indicate that melanophores of jaguar/obelix mutant fish have a defect in the signaling pathway downstream of the alpha2-adrenoceptor. Taken together, our results suggest that the cellular defect of the Kir7.1 mutation is directly responsible for the pattern change in the jaguar/obelix mutant.

Adrenergic Agonists↗

Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene.

Leopard, a well-known zebrafish mutant that has a spotted skin pattern instead of stripes, is a model for the study of pigment patterning. To understand the mechanisms underlying stripe formation, as well as the spot variation observed in leopard, we sought to identify the gene responsible for this phenotype. Using positional cloning, we identified the leopard gene as an orthologue of the mammalian connexin 40 gene. A variety of different leopard alleles, such as leo(t1), leo(tq270) and leo(tw28), show different skin-pattern phenotypes. In this manuscript we show that the mutation in allele leo(t1) is a nonsense mutation, whereas alleles leo(tq270) and leo(tw28) contain the missense mutations I202F and I31F, respectively. Patch-clamp experiments of connexin hemichannels demonstrated that the I202F substitution in allele leo(tq270) disrupted the channel function of connexin41.8. These results demonstrate that mutations in this gene lead to a variety of leopard spot patterns.

Alleles↗

Noise-resistant and synchronized oscillation of the segmentation clock.

Periodic somite segmentation in vertebrate embryos is controlled by the 'segmentation clock', which consists of numerous cellular oscillators. Although the properties of a single oscillator, driven by a hairy negative-feedback loop, have been investigated, the system-level properties of the segmentation clock remain largely unknown. To explore these characteristics, we have examined the response of a normally oscillating clock in zebrafish to experimental stimuli using in vivo mosaic experiments and mathematical simulation. We demonstrate that the segmentation clock behaves as a coupled oscillator, by showing that Notch-dependent intercellular communication, the activity of which is regulated by the internal hairy oscillator, couples neighbouring cells to facilitate synchronized oscillation. Furthermore, the oscillation phase of individual oscillators fluctuates due to developmental noise such as stochastic gene expression and active cell proliferation. The intercellular coupling was found to have a crucial role in minimizing the effects of this noise to maintain coherent oscillation.

Animals↗

Pigment cell distributions in different tissues of the zebrafish, with special reference to the striped pigment pattern.

The orderly pigment pattern of zebrafish (Danio rerio) is a good model system for studying how spatial patterns form in animals. Recent molecular genetic studies have shown that interactions between the pigment cells play major roles in pattern formation. In the present study, we performed comparative transmission electron microscopy of pigment cells, in order to clarify the structural interactions of pigment cells in tissues with and without a striped pattern. In patterned tissues, pigment cells were distributed as a one-cell-thick sheet. The layer order of the sheets is always kept strictly. In tissues without a striped pattern, the layer order was often disturbed or the cells were distributed in a scattered, double-sheeted, or an accumulated pile. Our observations suggest that the underlying mechanism that controls the vertical order of the pigment cells is related to that controlling the stripe pattern.

Animals↗

Stripes, spots, or reversed spots in two-dimensional Turing systems.

Two-dimensional Turing models can generate stationary striped patterns or spotted patterns, and are used to explain the body pattern formation of animals. We studied the effects of the choice of reaction terms on pattern selection, i.e., which pattern is likely to be formed. We examined in detail a model with linear reaction terms and additional constraint terms that confine two variables within a finite range. In the one-dimensional model, a periodic stationary pattern can be formed only when the activator level is constrained both from below and from above. In the two-dimensional model, the relative distance of the equilibrium level of the activator between the upper and lower limitations determines the pattern selection. Striped patterns are produced when the equilibrium is equally distant from the upper and the lower limitations, but spotted patterns are produced when the equilibrium is clearly closer to one than to the other of two limitations. We then examined models with nonlinear reaction terms, including both activator-inhibitor and activator-depletion substrate type models; we attempted to explain the pattern selection of these nonlinear models based on the results of linear models with constraints. The distribution of the activator level is skewed positively and negatively for spotted patterns and reversed spotted patterns, respectively. In contrast, the skew of the distribution of the activator level was close to zero in the case of striped patterns. This observation provides a heuristic argument of how the location of the equilibrium between the constraints leads to pattern selection.

Animals↗

Traveling stripes on the skin of a mutant mouse.

In the course of animal development, complex structures form autonomously from the apparently shapeless egg. How cells can produce spatial patterns that are much larger than each cell is one of the key issues in developmental biology. It has been suggested that spatial patterns in animals form through the same principles by which dispatched structures are formed in the nonbiological system. However, because of the complexity of biological systems, molecular details of such phenomena have been rarely clarified. In this article, we introduce an example of a pattern-forming phenomenon that occurs in the skin of mutant mice. The mutant mouse has a defect in splicing of the Foxn1 (Whn or nude) gene, which terminates hair follicle development just after pigment begins to accumulate in the follicle. The immature follicles are rapidly discharged, and a new hair cycle resumes. Eventually, the skin color of the mouse appears to oscillate. The color oscillation is synchronous in juvenile mice, but the phase gradually shifts among skin regions to eventually form traveling, evenly spaced stripes. Although the time scale is quite different, the pattern change in the mutant mouse shares characteristics with the nonlinear waves generated on excitable media, such as the Belousov-Zhabotinskii reaction, suggesting that a common principle underlies the wave pattern formation. Molecular details that underlie the phenomenon can be conjectured from recent molecular studies.

Age Factors↗

Origin of directionality in the fish stripe pattern.

The formation of stripe patterns in animal skin has been explained by the reaction-diffusion (RD) system, a hypothetical chemical reaction proposed by A. Turing. Although animal stripes usually have directionality, the RD model alone cannot explain how the direction is specified. To investigate the mechanism regulating the direction of stripes, we studied stripe pattern formation in two species of Genicanthus during sexual conversion. These species share almost identical morphologic properties, except for their stripe direction. In both species, spots transiently arise at random positions and then combine and rearrange to form directional stripes. Computational analysis has shown that diffusion anisotropy is very effective at specifying the direction of stripes formed by the RD system. Model simulations reproduce the transient dynamics of directional pattern formation observed in fish as well as the resulting stripes. In cases where the magnitude and direction of diffusion anisotropy of the substances are identical, the resulting stripes are not directional. However, if they differ, stripes become directional. As only a small difference in anisotropy is required for this effect, any kind of structure with directional conformation might cause a marked change in stripe direction. Scales are the most likely candidate structure for generating anisotropic interactions in skin.

Animals↗

Pigment cell organization in the hypodermis of zebrafish.

Zebrafish have a characteristic horizontal-stripe pigment pattern made by a specific distribution of three types of pigment cells: melanophores, xanthophores, and iridophores. This pattern is a valuable model to investigate how the spatial patterns form during animal development. Although recent findings suggest that the interactions among the pigment cells play a key role, the particular details of these interactions have not yet been clarified. In this report, we performed transmission electron microscopic study to show the distribution, conformation, and how the cells contact with each other in the hypodermis. We found that the pigment cells form complex but ordered, layered structures in both stripe and interstripe regions. The order of the layered structures is kept strictly all through the hypodermal regions. Our study will provide basic information to investigate the mechanism of pigment pattern formation in zebrafish.

Animals↗

Directionality of stripes formed by anisotropic reaction-diffusion models.

Turing mechanism explains the formation of striped patterns in a uniform field in which two substances interact locally and diffuse randomly. In a twin paper, to explain the directionality of stripes on fish skin in closely related species, we studied the effect of anisotropic diffusion of the two substances on the direction of stripes, in the cases in which both substances have high diffusivity in the same direction. In this paper, we study the direction of stripes in more general situations in which the diffusive direction may differ between the two substances. We derive a formula for the direction of stripes, based on a heuristic argument of unstable modes of deviation from the uniform steady state. We confirm the accuracy of the formula by computer simulations. When the diffusive direction is different between two substances, the directions of stripes in the spatial pattern change smoothly with the magnitude of anisotropy of two substances. When the diffusive direction of the two substances is the same, the stripes are formed either parallel or perpendicular to the common diffusive direction, depending on the relative magnitude of the anisotropy. The transition between these two phases occurs sharply.

Animals↗

The reaction-diffusion system: a mechanism for autonomous pattern formation in the animal skin.

How do animals acquire their various skin patterns? Although this question may seem easy, in fact it is very difficult to answer. The problem is that most animals have no related structures under the skin; therefore, the skin cells must form the patterns without the support of a prepattern. Recent progress in developmental biology has identified various molecular mechanisms that function in setting the positional information needed for the correct formation of body structure. None of these can explain how skin pattern is formed, however, because all such molecular mechanisms depend on the existing structure of the embryo. Although little is known about the underlying molecular mechanism, many theoretical studies suggest that the skin patterns of animals form through a reaction-diffusion system-a putative 'wave' of chemical reactions that can generate periodic patterns in the field. This idea had remained unaccepted for a long time, but recent findings on the skin patterns of fish have proved that such waves do exist in the animal body. In this review, we explain briefly the principles of the reaction-diffusion mechanism and summarize the recent progress made in this area.

Animals↗