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Loss of fish actinotrichia proteins and the fin-to-limb transition


The early development of teleost paired fins is strikingly similar to that of tetrapod limb buds and is controlled by similar mechanisms1,2. One early morphological divergence between pectoral fins and limbs is in the fate of the apical ectodermal ridge (AER), the distal epidermis that rims the bud. Whereas the AER of tetrapods regresses after specification of the skeletal progenitors3, the AER of teleost fishes forms a fold that elongates4,5. Formation of the fin fold is accompanied by the synthesis of two rows of rigid, unmineralized fibrils called actinotrichia, which keep the fold straight6,7 and guide the migration of mesenchymal cells within the fold5,8. The actinotrichia are made of elastoidin, the components of which, apart from collagen, are unknown. Here we show that two zebrafish proteins, which we name actinodin 1 and 2 (And1 and And2), are essential structural components of elastoidin. The presence of actinodin sequences in several teleost fishes and in the elephant shark (Callorhinchus milii, which occupies a basal phylogenetic position), but not in tetrapods, suggests that these genes have been lost during tetrapod species evolution. Double gene knockdown of and1 and and2 in zebrafish embryos results in the absence of actinotrichia and impaired fin folds. Gene expression profiles in embryos lacking and1 and and2 function are consistent with pectoral fin truncation and may offer a potential explanation for the polydactyly observed in early tetrapod fossils. We propose that the loss of both actinodins and actinotrichia during evolution may have led to the loss of lepidotrichia and may have contributed to the fin-to-limb transition.

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Figure 1: Schematic representations of the zebrafish and elephant shark actinodin proteins.
Figure 2: Expression of and1 correlates with the growth of actinotrichia.
Figure 3: Double gene knockdown of and1 and and2 leads to an absence of actinotrichia and reduced or absent fin folds.
Figure 4: Gene expression analysis in pectoral fin buds of double and morphants.


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The authors would like to thank I. Duran for technical advice, A. Maurya for assistance in the early stages of this work and M. Ekker, F. Avaron and M. Debiais for discussions and critical reading of the manuscript. L.S.-P. is supported by a European Modular Biology Organization Long-Term Fellowship (ALT 325-2008). This work was supported by grants to M.-A.A. from the Natural Science Engineering and Research Council of Canada and the Canadian Institutes of Health Research. M.A.A.-N. received funding from the Canada Research Chairs programme and from the Helmholtz Alliance on Systems Biology. V.K. received funding from the Agency for Science, Technology and Research of Singapore.

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J.Z., P.W., D.G. and B.K.P. performed the experiments; J.Z. collected and analysed the data; V.K. produced and provided the enhancer-trap transgenic line; M.A.A.-N. and L.S.-P. performed the analysis of the actinodin sequences; and M.-A.A. designed experiments, analysed data and wrote the manuscript.

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Correspondence to Marie-Andrée Akimenko.

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The authors declare no competing financial interests.

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Zhang, J., Wagh, P., Guay, D. et al. Loss of fish actinotrichia proteins and the fin-to-limb transition. Nature 466, 234–237 (2010).

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