Linking genotype, cell behavior, and phenotype: multidisciplinary perspectives with a basis in zebrafish patterns
Introduction
Because alterations in cellular dynamics lead to differences in organism appearance, pattern formation on animal skin is a useful system for studying cell behavior. Amenable to many experimental techniques and widely used for its biomedical applications, the zebrafish (Danio rerio) is a model organism for exploring pattern formation [1, 2, 3, 4]. Zebrafish are characterized by dark stripes and light interstripes, but diverse patterns are found in mutant fish [1,2,5]. These patterns form due to the interactions of tens of thousands of brightly colored pigment cells.
Writing for an interdisciplinary audience, in this review I discuss how experimental and mathematical-modeling approaches are being used to identify the genetic and cellular differences that underlie different phenotypes, linking scales that span from intracellular to evolutionary (Figure 1). With a focus on the literature from the last three years, I review self-organization in zebrafish, describe different modeling approaches to collective cell dynamics, highlight findings on the mechanisms that underlie cell communication, and discuss multidisciplinary perspectives on new pattern formation frontiers, including zebrafish's siblings in the Danio genus [9,10••,11], clownfish [12•], and lizards [13••].
Section snippets
Biology of self-organization
There are three main types of pigment cells that are involved in pattern formation in zebrafish: black melanophores (or melanocytes), yellow/orange xanthophores, and iridescent silver/blue iridophores. These cells belong to a wider set of chromatophores that are present in fish (and other cold-blooded animals) and also includes red erythrophores, white leucophores, and blue cyanophores [1,12•]. Interestingly, Lewis et al. [17••] recently showed that a subclass of leucophores develops from
Mathematics of self-organization
Mathematical biologists have used three main approaches to describe wild-type and mutant pattern formation in zebrafish (Figure 3). On the microscopic side, agent-based models treat cells as individuals and track the -coordinate of each cell's center (Figure 3b). Cells move continuously in space on growing domains according to differential equations, and stochastic rules govern differentiation, competition, and transitions in form [16,30]. Cellular automaton models [29,31], in comparison,
Mechanisms of cell communication
Down a scale from collective dynamics and phenomenological models, we can ask about the mechanisms that underlie how cells communicate, change their shape, and determine their fate. This is a complex and exciting problem, and I overview some of the ways that chromatophores interact in zebrafish.
Gap junctions are a form of communication between adjacent cells that can be thought of as cellular handshakes (Figure 4a–c). Each cell offers a connexon (e.g. hand) to form the channel, and individual
Diversity of patterns
There are several lines of new work that involve taking a broader view of pattern formation. If we look at zebrafish as a whole, there are differences in the patterns that appear in different regions of the fish [8,9,21]. For example, Eskova et al. [23•] recently showed that chromatophores from mau mutant zebrafish (encoding Aqp3a) can produce stripes when transplanted to a wild-type environment, highlighting the role of the tissue environment in pattern formation [21] (Figure 5a). Moreover,
Conclusions
The zebrafish (Danio rerio) is a widely studied, experimentally tractable fish with important biomedical applications [1, 2, 3,46]. Within this species, there is a broad range of mutant patterns that form as the fish grows due to cell interactions that have been altered (often in unknown ways). Because they have been extensively studied in the lab, there is a wealth of biological literature available on zebrafish, and mathematicians [16,31,33] have used this to build models that make
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
I am especially grateful to Uwe Irion and Richard Carthew for answering my questions from a biological perspective and for their comments on a draft of this review. More broadly, I also thank the community of zebrafish experimentalists that I have been fortunate to meet and learn from for invaluable conversations that have added to my perspective on zebrafish over time. This work has been supported by the National Science Foundation under grant no. DMS-1764421 and by the Simons Foundation/SFARI
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