1. Developmental Biology
  2. Evolutionary Biology
Download icon

Patterning: Fishing for ancestry

  1. Hannah Brunsdon  Is a corresponding author
  2. E Elizabeth Patton  Is a corresponding author
  1. MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom
Insight
  • Cited 1
  • Views 1,703
  • Annotations
Cite this article as: eLife 2018;7:e39524 doi: 10.7554/eLife.39524

Abstract

The same genes and signalling pathways control the formation of skin appendages in both fish and land animals.

Main text

The tough scales found on alligators, the colourful feathers of peacocks and the thick fur of polar bears are all examples of skin appendages – self-contained mini-organs that form a barrier between an organism and its environment (Chuong et al., 2013). These skin appendages are essential for providing protection, retaining heat, sensing movement, attracting mates and, in some animals, flying. How these immensely complex and diverse structures have evolved, and how they develop, has fascinated researchers for decades.

Due to the sheer variety of skin appendages in both living and fossilised animals, it is still unclear whether they evolved independently or from a common ancestor (Dhouailly et al., 2017). However, as some of the earliest processes involved in the development of feathers and hair are very similar, the basic genetic mechanisms underlying their formation could have shared evolutionary origins (Musser et al., 2015). Indeed, researchers recently found that the cell signalling events involved in the development of scales in reptiles and the events regulating the patterning of appendages in birds and mammals have many similarities (Di-Poï and Milinkovitch, 2016). For example, slightly altering gene expression in reptile scales or the scaly foot of a chicken can lead to the formation of feather buds and primitive feathers respectively, akin to those found in dinosaurs (Wu et al., 2018).

Therefore, it seems likely that the skin appendages of reptiles, birds and mammals – collectively known as amniotes – have a shared evolutionary origin. Fish scales appear to be different in that they are made of bone instead of keratin, and also derive from a different layer of skin. However, is it possible that amniotes and fish share a common, ancestral skin appendage that existed even further back in time than was previously thought? Now, in eLife, Andrew Aman, Alexis Fulbright and David Parichy of the University of Virginia report the results of experiments on zebrafish which suggest that this might be the case (Aman et al., 2018).

Through beautifully detailed live imaging of developing scales and the manipulation of key signalling pathways during their development, Aman et al. were able to study how zebrafish scales form and arrange themselves correctly on the skin. The first hint that appendage patterning in fish is similar to that of amniotes came from close observation of scale development, which occurred sequentially in a hexagonal grid pattern to cover the fish, a patterning strategy shared with the land animals.

Aman et al. then investigated whether the cell signalling mechanisms underpinning these morphological events might also be conserved at the molecular level. In all amniote species investigated so far, the earliest signalling event in appendage formation is the activation of the Wnt signalling pathway, which regulates many aspects of cell development and behaviour. Using genetically modified fish to highlight Wnt-signalling cells, it was possible to identify clusters of cells congregating at sites that would later form scales. Aman et al. showed that Wnt signalling and the subsequent activation of another signalling pathway, the Eda pathway, were both necessary for the scales to develop, and that blocking either pathway caused a complete loss of scale formation. This skin appendage loss is consistent with the one observed in fish, bearded lizards, chicks, mice and humans with defective Eda signalling (Harris et al., 2008; Sennett and Rendl, 2012; Drew et al., 2007; Di-Poï and Milinkovitch, 2016).

Next, Aman et al. disrupted combinations of these and other signalling systems known to be involved in the development of skin appendages in amniotes, to expand our knowledge of appendage development. These experiments revealed that, similar to birds and mammals, another signalling system that is important for the development and repair of cells, the fibroblast growth factor system, was required for the scales to differentiate further (Mandler and Neubüser, 2004; Huh et al., 2013). Moreover, the researchers discovered a new role for another well-known signalling system, the Sonic hedgehog system, which instructed the top layer of the skin to fold over the scales, similar to the skin movements that occur as hair follicles develop (St-Jacques et al., 1998). These similarities hint at the existence of a single, ancient origin of appendage patterning in vertebrates (Figure 1).

Simplified schematic illustrating the development of skin appendages.

The development of skin appendages is initiated by the activation of the Wnt signalling pathway in the top layer of the skin (the epidermis), and this signal is refined and maintained by the Eda signalling pathway. Both systems activate two further pathways that are important for cell growth and development: fibroblast growth factor (Fgf) signalling is necessary to ensure that the patterning of the appendages happens correctly and that scales are able to form; the Sonic hedgehog pathway ensures that the epidermis folds properly over the scales. Fish scales are formed from bone, whereas feathers, reptile scales and hair are formed from keratin. However, over time a common ancestor may have stopped using bone and started using keratin to build skin appendages in amniotes.

Discovering such conserved gene regulatory networks in the zebrafish – an organism that is so readily amenable to high-resolution imaging and genetic manipulation – is very exciting. In amniotes, these fleeting events mainly occur in the womb or egg, which makes it difficult to collect stage-matched animals and use live imaging – a challenge in identifying key signalling processes (Sennett and Rendl, 2012).

If we could further untangle the contribution of various genes involved in the development of skin appendages, we might be able to apply this knowledge to tissue engineering (by, for example, regulating hair patterning on skin grafts). Also, by identifying new genes or functions of genes in appendage development, zebrafish could help us understand and ultimately treat skin disorders in humans.

References

Article and author information

Author details

  1. Hannah Brunsdon

    Hannah Brunsdon is in the MRC Human Genetics Unit & Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

    For correspondence
    Hannah.Brunsdon@igmm.ed.ac.uk
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8363-6500
  2. E Elizabeth Patton

    E Elizabeth Patton is in the MRC Human Genetics Unit & Cancer Research UK Edinburgh Cancer, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

    For correspondence
    e.patton@igmm.ed.ac.uk
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2570-0834

Publication history

  1. Version of Record published: August 2, 2018 (version 1)

Copyright

© 2018, Brunsdon et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,703
    Page views
  • 127
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Christoph Budjan et al.
    Research Article

    During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM), and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm development such as the human segmentation clock in vitro using human pluripotent stem cells (hPSCs), however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human paraxial mesoderm (PM) organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological and functional features of paraxial mesoderm development, including formation of somite-like structures in vitro. Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their in vivo counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spinal cord development and disease in vitro.

    1. Developmental Biology
    Ruth M Williams et al.
    Tools and Resources

    The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harboring neural crest and cranial placode progenitors. Here, we a generate single-cell atlas of the developing chick epiblast from late gastrulation through early neurulation stages to define transcriptional changes in the emerging ‘neural plate border’ as well as other regions of the epiblast. Focusing on the border territory, the results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridization. Developmental trajectory analysis infers that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined neural crest and placode lineages. The data also can be mined to reveal changes throughout the developing epiblast.