Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development

Andrew J Aman, Alexis N Fulbright, David M Parichy

Preprint posted on 2 April 2018

Article now published in eLife at

Analysis of zebrafish scale development suggests a common ancient origin of the molecular machinery controlling the basic patterning of skin appendages in vertebrates.

Selected by Andreas van Impel


During amniote development, the ectoderm gives rise to various characteristic skin appendages including hair, teeth, mammary and exocrine glands in mammals, feathers in birds and scales in reptiles. Despite the obvious differences in their final form and function, these distinct ectodermal appendages share common developmental features, leading to the idea that they are all evolutionary derived from a common ancestral progenitor in early amniotes. But might such appendages have deeper evolutionary origins? Outside of the amniotes, another type of skin appendage are the calcified scales of fish. Although the development of these scales has been shown to be sensitive to several players that are also involved in amniote ectoderm appendage formation, it is not clear at present whether teleost scales and amniote skin appendages are homologous structures that evolved from a common ancestor.


Key findings

In the current preprint, Aman and colleagues employ zebrafish larvae to investigate the genetic program involved in scale development. Since fish scales are characterized by a calcified composition, the authors hypothesized that osteoblast-like cells would be involved in their formation. Using transgenic reporter fish for the osteoblast marker sp7/osterix combined with Alizarin Red vital staining of calcified extracellular matrix, they identify sp7-positive cell clusters in the dermis at sites where the deposition of calcified matrix can be detected shortly after, and where ultimately a new scale will form. Making use of these live imaging tools, the authors show that similar to skin appendages in amniotes, the scale primordia are added in a sequential fashion giving rise to a tightly packed hexagonal grid within about 13 days (see figure).

During squamation in zebrafish, scale-forming cells (sp7:eGFP in yellow) appear in a sequential pattern at sites in the skin, where shortly after calcified matrix (Alizarin Red in purple) is detectable and a new scale will be formed (Reproduced from Fig.1, Aman et al.).


In order to find out whether the signaling pathways involved in amniote skin appendage development are also required for scale formation, Aman et al. initially focus on Wnt/ß-catenin signaling, a pathway that has been shown to be essential for the induction of ectodermal appendages in amniotes. In line with such an early requirement, conditional blockage of Wnt signaling completely prevents scale initiation. Furthermore and again very similar to the situation in amniotes, the authors find that Eda, FGF and Hh signaling are all involved in different steps of scale development, suggesting that a common set of core signaling pathways is employed in all vertebrates during skin appendage development.


Why this is cool

What I like about this preprint from the Parichy lab is that it nicely combines zebrafish developmental biology with an evolutionary biology question. Their beautiful imaging of scale formation in vivo (see figure) not only indicates that the sequence of squamation in zebrafish resembles that of other fishes like medaka, but that it is strikingly similar to the ordered addition of feathers in chicken or the scale anlagen in reptiles. On the molecular level, Aman et al. identify a requirement for Wnt, Eda, Fgf and Hh signalling pathways and describe various interactions between those during scale induction and morphogenesis. Since the same regulatory network also controls skin appendage formation in amniotes, the results support the idea that the basic machinery controlling the patterning of skin appendages is conserved between extant vertebrates and originate already from a common pre-amniotic ancestor.


Further directions

Despite the obvious differences in the final output of ectodermal appendage formation in teleosts and amniotes, the apparent conservation of signalling events controlling the initiation, patterning and early morphogenesis of these appendages render the zebrafish – with all its advantages like the exceptional live cell imaging possibilities and the enormous toolbox for forward and reverse genetic approaches – a very attractive additional model system to further unravel the molecular control during vertebrate skin patterning.


Further reading

Biggs LC, Mikkola ML (2014) Early inductive events in ectodermal appendage morphogenesis. Semin Cell Dev Biol, Vol25-26: 11-21

Di-Poï N, Milinkovitch NC (2016) The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes. Sci Adv.; 2(6): e1600708

Harris MP, Rohner N, Schwarz H, Perathoner S, Konstantinidis P, Nüsslein-Volhard C. (2008) Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates. PLoS Genet.; 4(10):e1000206

Tags: bone, calcification, danio rerio, evolution

Posted on: 26 April 2018

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