Sonic hedgehog function in chondrichthyan fins and the evolution of appendage patterning

Abstract

The genetic mechanisms regulating tetrapod limb development are well characterized, but how they were assembled during evolution and their function in basal vertebrates is poorly understood. Initial studies report that chondrichthyans, the most primitive extant vertebrates with paired appendages, differ from ray-finned fish and tetrapods in having Sonic hedgehog (Shh)-independent patterning of the appendage skeleton1. Here we demonstrate that chondrichthyans share patterns of appendage Shh expression, Shh appendage-specific regulatory DNA, and Shh function with ray-finned fish and tetrapods2,3,4,5,6,7,8,9,10. These studies demonstrate that some aspects of Shh function are deeply conserved in vertebrate phylogeny, but also highlight how the evolution of Shh regulation may underlie major morphological changes during appendage evolution.

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Figure 1: Shh is expressed in wild-type and retinoic acid (RA)-treated basal vertebrate appendages.
Figure 2: Retinoic acid effects dose- and stage-dependent fin skeleton alterations in chondrichthyans.
Figure 3: Retinoic acid induces ectopic elements and posteriorizes skate fin structures.

References

  1. 1

    Tanaka, M. et al. Fin development in a cartilaginous fish and the origin of vertebrate limbs. Nature 416, 527–531 (2002)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401–1416 (1993)

    CAS  Article  Google Scholar 

  3. 3

    Krauss, S., Concordet, J. P. & Ingham, P. W. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431–1444 (1993)

    CAS  Article  Google Scholar 

  4. 4

    Akimenko, M. A. & Ekker, M. Anterior duplication of the Sonic hedgehog expression pattern in the pectoral fin buds of zebrafish treated with retinoic acid. Dev. Biol. 170, 243–247 (1995)

    CAS  Article  Google Scholar 

  5. 5

    Hoffman, L., Miles, J., Avaron, F., Laforest, L. & Akimenko, M. A. Exogenous retinoic acid induces a stage-specific, transient and progressive extension of Sonic hedgehog expression across the pectoral fin bud of zebrafish. Int. J. Dev. Biol. 46, 949–956 (2002)

    CAS  PubMed  Google Scholar 

  6. 6

    Tickle, C., Alberts, B., Wolpert, L. & Lee, J. Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296, 564–566 (1982)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Sagai, T., Hosoya, M., Mizushina, Y., Tamura, M. & Shiroishi, T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development 132, 797–803 (2005)

    CAS  Article  Google Scholar 

  8. 8

    Lettice, L. A. et al. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 12, 1725–1735 (2003)

    CAS  Article  Google Scholar 

  9. 9

    Sagai, T. et al. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog (Shh). Mamm. Genome 15, 23–34 (2004)

    CAS  Article  Google Scholar 

  10. 10

    Maas, S. A. & Fallon, J. F. Single base pair change in the long-range Sonic hedgehog limb specific enhancer is a genetic basis for preaxial polydactyly. Dev. Dyn. 232, 345–348 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Ballard, W. W., Mellinger, J. & Lechenault, H. A series of normal stages for development of Scyliorhinus canicula, the lesser spotted dogfish (Chondrichthyes: Scyliorhinidae). J. Exp. Zool. 267, 318–336 (1993)

    Article  Google Scholar 

  12. 12

    Pearse, R. V., Vogan, K. J. & Tabin, C. J. Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling activity during chick embryogenesis. Dev. Biol. 239, 15–29 (2001)

    CAS  Article  Google Scholar 

  13. 13

    Vandersea, M. W., Fleming, P., McCarthy, R. A. & Smith, D. G. Fin duplications and deletions induced by disruption of retinoic acid signaling. Dev. Genes Evol. 208, 61–68 (1998)

    CAS  Article  Google Scholar 

  14. 14

    Chiang, C. et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev. Biol. 236, 421–435 (2001)

    CAS  Article  Google Scholar 

  15. 15

    Ros, M. A. et al. The chick oligozeugodactyly (ozd) mutant lacks sonic hedgehog function in the limb. Development 130, 527–537 (2003)

    CAS  Article  Google Scholar 

  16. 16

    Gritli-Linde, A., Lewis, P., McMahon, A. P. & Linde, A. The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. Dev. Biol. 236, 364–386 (2001)

    CAS  Article  Google Scholar 

  17. 17

    Saunders, J. W. & Gasseling, M. T. Epithelial Mesenchymal Interactions (eds Fleischmajer, A. and Billingham, R. E.) 78–97 (William and Wilkins, Baltimore, 1968)

    Google Scholar 

  18. 18

    Davis, M. C., Shubin, N. H. & Force, A. Pectoral fin and girdle development in the basal actinopterygians Polyodon spathula and Acipenser transmontanus. J. Morphol. 262, 608–628 (2004)

    Article  Google Scholar 

  19. 19

    Bemis, W. E. & Grande, L. Early development of the actinopterygian head. I. External development and staging of the paddlefish Polyodon spathula. J. Morphol. 213, 47–83 (1992)

    CAS  Article  Google Scholar 

  20. 20

    Prince, V. E., Joly, L., Ekker, M. & Ho, R. K. Zebrafish hox genes: genomic organization and modified colinear expression patterns in the trunk. Development 125, 407–420 (1998)

    CAS  PubMed  Google Scholar 

  21. 21

    Dahn, R. D. & Fallon, J. F. Interdigital regulation of digit identity and homeotic transformation by modulated BMP signaling. Science 289, 438–441 (2000)

    ADS  CAS  Article  Google Scholar 

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Acknowledgements

We thank A. Tullis of The University of Puget Sound, Marine Biological Laboratories at Woods Hole, K. Riley of Chicago Aquarium and Pond for specimens, K. Tamura and T. Sagai for sharing unpublished data, P. Beachy for assistance, and K. Monoyios for illustration and graphics assistance. This work was supported by fellowships from The National Institutes of Health (R.D.D.), The Jane Coffin Childs Memorial Fund for Medical Research (W.N.P.), and the Division of Biological Sciences at The University of Chicago (N.H.S.).

Author Contributions All experiments were designed and data generated by R.D.D., except for isolation of full-length skate Shh cDNA (W.N.P.) and the Polyodon data (M.C.D.). Data were analysed and the manuscript prepared by R.D.D. and N.H.S.

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Correspondence to Neil H. Shubin.

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

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Dahn, R., Davis, M., Pappano, W. et al. Sonic hedgehog function in chondrichthyan fins and the evolution of appendage patterning. Nature 445, 311–314 (2007). https://doi.org/10.1038/nature05436

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