The Turing, or reaction-diffusion (RD), model is one of the best-known theoretical models used to explain self-regulated pattern formation in the developing animal embryo. Although its real-world ...relevance was long debated, a number of compelling examples have gradually alleviated much of the skepticism surrounding the model. The RD model can generate a wide variety of spatial patterns, and mathematical studies have revealed the kinds of interactions required for each, giving this model the potential for application as an experimental working hypothesis in a wide variety of morphological phenomena. In this review, we describe the essence of this theory for experimental biologists unfamiliar with the model, using examples from experimental studies in which the RD model is effectively incorporated.
Pigment patterns of organisms have invoked strong interest from not only biologists but also, scientists in many other fields. Zebrafish is a useful model animal for studying the mechanism of pigment ...pattern formation. The zebrafish stripe pattern is primarily two types of pigment cells: melanophores and xanthophores. Previous studies have reported that interactions among these pigment cells are important for pattern formation. In the recent report, we found that the direct contact by xanthophores induces the membrane depolarization of melanophores. From analysis of jaguar mutants, it is suggested that the depolarization affects the movements of melanophores. To analyze the cell movement in detail, we established a unique in vitro system. It allowed us to find that WT xanthophores induced repulsive movement of melanophores through direct contact. The xanthophores also chased the melanophores. As a result, they showed run-and-chase movements. We also analyzed the cell movement of pigment cells from jaguar and leopard mutants, which have fuzzy stripes and spot patterns, respectively. jaguar cells showed inhibited run-and-chase movements, and leopard melanophores scarcely showed repulsive response. Furthermore, we paired mutant and WT cells and showed which of the melanophores and xanthophores have responsibility for the altered cell movements. These results suggested that there is a correspondence relationship between the cell movements and pigment patterns. The correspondence relationship highlighted the importance of the cell movements in the pattern formation and showed that our system is a quite useful system for future study in this field.
Studies of Turing pattern formation in zebrafish skin Kondo, Shigeru; Watanabe, Masakatsu; Miyazawa, Seita
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
12/2021, Volume:
379, Issue:
2213
Journal Article
Peer reviewed
Open access
Skin patterns are the first example of the existence of Turing patterns in living organisms. Extensive research on zebrafish, a model organism with stripes on its skin, has revealed the principles of ...pattern formation at the molecular and cellular levels. Surprisingly, although the networks of cell-cell interactions have been observed to satisfy the 'short-range activation and long-range inhibition' prerequisites for Turing pattern formation, numerous individual reactions were not envisioned based on the classical reaction-diffusion model. For example, in real skin, it is not an alteration in concentrations of chemicals, but autonomous migration and proliferation of pigment cells that establish patterns, and cell-cell interactions are mediated via direct contact through cell protrusions. Therefore, the classical reaction-diffusion mechanism cannot be used as it is for modelling skin pattern formation. Various studies are underway to adapt mathematical models to the experimental findings on research into skin patterns, and the purpose of this review is to organize and present them. These novel theoretical methods could be applied to autonomous pattern formation phenomena other than skin patterns. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.
To investigate the spatiotemporal dynamics of skin pattern formation, we developed a simple method for artificially disarranging the placement of all three pigment cell types in the body trunk of ...zebrafish (Danio rerio). We generated transgenic fish with melanophores that ectopically expressed a variant of channelrhodopsin-2 (ChR2). Blue light (BL) irradiation induced melanophore depolarization and random migration; the latter resulted in the disarrangement of the two other pigment cell types (xanthophores and iridophores). This BL disarrangement (BLD) method was effective in both young and adult fish, but it did not affect the initial placement of pigment cells in juvenile fish (approximately 5 weeks post-fertilization). Irradiation with BL was not harmful to cells, and the patterning process immediately resumed when BL was switched off. Using the BLD method, we demonstrated that interactions between pigment cells determined stripe width in the absence of any pre-set positional cues, while the initial horizontal alignment of iridophores determined their directionality. The BLD method can be adapted to any zebrafish skin-pattern mutant, providing a novel tool for analyzing pattern formation mechanisms under a variety of conditions and facilitating further study in this field.
•Using optogenetics, we constructed a method to noninvasively disarrange the skin pattern of zebrafish.•This method provides a new procedure to analyze the mechanism of skin pattern formation.•The initial positional cue just determines the stripe directionality, and the width of stripes is autonomously determined.
Although recent experimental studies have suggested that the interactions among the pigment cells play a key role in the skin pattern formation, details of the mechanism remain largely unknown. By ...using an in vitro cell culture system, we have detected interactions between the two pigment cell types, melanophores and xanthophores, in the zebrafish skin. During primary culture, the melanophore membrane transiently depolarizes when contacted with the dendrites of a xanthophore. This depolarization triggers melanophore migration to avoid further contact with the xanthophores. Cell depolarization and repulsive movement were not observed in pigment cells with the jaguar mutant, which shows defective segregation of melanophores and xanthophores. The depolarization-repulsion of wild-type pigment cells may explain the pigment cell behaviors generating the stripe pattern of zebrafish.
The reaction-diffusion system is one of the most studied nonlinear mechanisms that generate spatially periodic structures autonomous. On the basis of many mathematical studies using computer ...simulations, it is assumed that animal skin patterns are the most typical examples of the Turing pattern (stationary periodic pattern produced by the reaction-diffusion system). However, the mechanism underlying pattern formation remains unknown because the molecular or cellular basis of the phenomenon has yet to be identified. In this study, we identified the interaction network between the pigment cells of zebrafish, and showed that this interaction network possesses the properties necessary to form the Turing pattern. When the pigment cells in a restricted region were killed with laser treatment, new pigment cells developed to regenerate the striped pattern. We also found that the development and survival of the cells were influenced by the positioning of the surrounding cells. When melanophores and xanthophores were located at adjacent positions, these cells excluded one another. However, melanophores required a mass of xanthophores distributed in a more distant region for both differentiation and survival. Interestingly, the local effect of these cells is opposite to that of their effects long range. This relationship satisfies the necessary conditions required for stable pattern formation in the reaction-diffusion model. Simulation calculations for the deduced network generated wild-type pigment patterns as well as other mutant patterns. Our findings here allow further investigation of Turing pattern formation within the context of cell biology.
Spear-like collagen complexes, known as actinotrichia, underlie the epidermal cell layer in the tip of teleost fins and are known to contribute toward fin formation; however, their specific role ...remains largely unclear. In this study, we investigated of actinotrichia in the role of caudal fin formation by generating collagen9a1c (col9a1c)-knockout zebrafish. Although actinotrichia were initially produced normally and aligned correctly in the knockout fish, the number of actinotrichia decreased as the fish grew and their alignment became disordered. Simultaneously, the fin tip gradually shortened in the dorsal-ventral direction and the entire fin became oval-shaped, while the fin-rays rarely bifurcated and instead underwent fusion, suggesting that actinotrichia are essential for spreading fins dorsoventrally. Furthermore, the epithelial cells that are usually thinly spread in normal fish became spherical in the knockout fish, reducing the area covered by each cell and thus the area of the fin tip. Together, these findings suggest that the tight alignment of actinotrichia provides physical support in the dorsal-ventral direction that allows caudal fins to expand in a triangular-shape.
•The physical role of collagen fibers called actinotrichia in caudal fin shape formation was investigated.•Actinotrichia are arranged in parallel to form a two-dimensional scaffold.•When the scaffold is lost, an extreme contraction of epithelial cells occurs.•The contraction of the epithelial cells is thought to shorten the fins along dorsal-ventral axis.
In multicellular organisms, cell properties, such as shape, size and function are important in morphogenesis and physiological functions. Recently, ‘cellular chirality’ has attracted attention as a ...cellular property because it can cause asymmetry in the bodies of animals. In recent in vitro studies, the left–right bias of cellular migration and of autonomous arrangement of cells under some specific culture conditions were discovered. However, it is difficult to identify the molecular mechanism underlying their intrinsic chirality because the left–right bias observed to date is subtle or is manifested in the stable orientation of cells. Here, we report that zebrafish (Danio rerio) melanophores exhibit clear cellular chirality by unidirectional counterclockwise rotational movement under isolated conditions without any special settings. The chirality is intrinsic to melanophores because the direction of the cellular rotation was not affected by the type of extracellular matrix. We further found that the cellular rotation was generated as a counter action of the clockwise movement of actin cytoskeleton. It suggested that the mechanism that directs actin cytoskeleton in the clockwise direction is pivotal for determining cellular chirality.
Ammonite shells have complex patterns of suture lines that vary across species. The lines are formed at the intersection of the outer shell wall and the septa. The wavy septa can form if the rear ...mantle of the ammonite, which functions as the template, has a complex shape. Previous hypotheses assumed that the rear mantle is like a flexible membrane that can be folded by some physical force. The elucidation of the mechanism of septa formation requires that the detailed shape of the septa should be known. We developed a new protocol of X-ray micro-computed tomography (CT) and obtained high-resolution three-dimensional (3D) images of the septa of the Upper Cretaceous ammonite Damesites cf. damesi. The obtained image suggested that the wavy and branched structures of the rear mantle grew autonomously. We found that some extant sea slugs have branched structures and showed similar shape and growth sequence as those in fossils, suggesting that the mantle of molluscs basically has the potential to form branched projections. Based on the characteristics of the obtained 3D structure, we explain how ammonites might have formed the complex suture patterns.
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