Symmetry breaking in the embryonic skin triggers a directional and sequential front of competence during plumage patterning

Richard Bailleul, Carole Desmarquet-Trin Dinh, Magdalena Hidalgo, Camille Curantz, Jonathan Touboul, Marie Manceau

Posted on: 21 December 2018

Preprint posted on 8 December 2018

Article now published in PLOS Biology at http://dx.doi.org/10.1371/journal.pbio.3000448

Feathers set the bar to study pattern formation: wonderful work combining a unified model and experimental data to recapitulate the complex sequence of events of plumage patterning #modeling #devbio #evodevo #preprint

Selected by Alexa Sadier

Categories: developmental biology, evolutionary biology, systems biology

Background

One of the key challenges of developmental biology is to explain how patterns arise and develop from a homogenous structure (such as skin) to give rise to complex organs (such as feathers) in a robust and reproducible manner. Research in the past few decades has revealed that patterning is a complex combination of differential gene expression, morphogenetic movements and mechano-chemical processes. As a result, modelling the establishment of a pattern from the beginning to the end has been challenging and most models consist of reproducing the final states of patterning events (e.g. spacing of hair, feather or teeth). In addition, these models are often limited to particular cases and are not able to explain how the diversity of motifs seen in nature can arise from pattern formation. To tackle this question, Bailleul and colleagues chose the example of bird plumage, looking at the patterning of tracts in which feathers are inserted. The interest of this choice is twofold. First, the events at the origin of feather tract patterning are well established in chicken, which allows its study from a modelling point of view with a good knowledge of the underlying mechanisms. Second, tracts and feathers are highly variable in terms of size, shape, number and pattern of emergence among species. For these reasons, the plumage of birds constitutes a perfect example to study these mechanisms and their variations.

Key findings

To build a realistic model that can explain both shared and variable mechanisms responsible for feather tract patterning, the authors first established the expression pattern of β-catenin transcript that is known to mark the early differentiation of feather follicles, in five different representative species of birds. This pattern of expression revealed the temporal dynamics of emergence of feather tracts and the pre-patterning events that initiate the lateral and sequential addition of new feathers in all the five species.

To identify the key parameters influencing tract patterning, the authors tested several classical patterning models separately. These models, such as classical reaction-diffusion mechanisms, chemotaxis or cell proliferation-based models, can each produce a pattern but fail to reproduce the pre-patterning and/or the sequential/directional addition of tracts rows, showing that multiple mechanisms are involved in the patterning process. To resolve this issue, they built a unified model combining these characteristics and tested it for each species or bird. Remarkably, simulations of this model based on a unique set of parameters for all the species, but with species-specific initial conditions, were able to recapitulate the formation of tracts in a bi-directional, row-by-row manner and with a realistic duration for all the five species of birds.

Then, they used this model to identify the events at the origin of the initial conditions observed in the different species. The resulting simulations revealed that the directional and sequential progression of tract differentiation results from a pre-pattern, and that this progression is due to a traveling front of increased cell density that defines the domains with self-organizing capacity.

Finally, the authors demonstrated the importance of cell proliferation, predicted by the model, for the duration of the patterning process by performing ex and in vivo experiments using BrdU or colchicine (which respectively labels and blocks cell proliferation). Altogether, these simulations and experimental results led to propose a complete scenario to explain the complex patterning of feather tracts and the origin of its variation in different species.

Why this work is important

This preprint sets the bar concerning the level of modelling and experimental data needed to completely describe pattern formation. While a lot of models consist of reproducing a snapshot of the final stage of a pattern, this one is able to recapitulate precisely all the steps of pattern formation, their dynamics and their duration.

Another important point of this preprint is the strength of the model that is able to reproduce accurately some key features of pattern formation, such as the temporal sequence, without resort to external forcing. The result is a unified and robust model that can be tuned and adapted to different scenarios, species and potentially other organs.

More broadly, this preprint fills a gap in our understanding of how repeated patterns are established and can be both extremely stable while allowing some variation in different species. This work is likely to be extended to other ectodermal appendages (for example: hair, scales, teeth, external glands or nails) and, to a certain extent, other replicated structures.

Future directions and questions for the authors

To what extent can this model be applied to other ectodermal appendages or, more broadly, repeated structures, that are known to share common patterning mechanisms?
Do you think that this model and the underlying developmental mechanisms constitute a developmental bias that constrains feather/ectodermal appendages evolution?
Aside from classical feather GRNs genes such as Wnt, Eda or Shh, do you expect cell proliferation genes or other factors to be involved in pattern formation and evolution?

Additional references

Kondo, S. & Miura, T. Reaction Diffusion as a framework for understanding biological pattern formation. Science 329, 1616-1620 (2010)
Painter,K.J., Hunt, G., Wells, K., Johanneson, K. & Headon, D.J. Towards an integrated experimental–theoretical approach for assessing the mechanistic basis of hair and feather morphogenesis. Interface Focus 2, 433-450 (2012)
Painter, K.J., Ho, W. & Headon, D.J. A chemotaxis model of feather primordia pattern formation during avian development. Journal of Theoretical Biology 437, 225-238 (2018)

Tags: development, ectodermal appendages, feather, patterning

doi: https://doi.org/10.1242/prelights.6754

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