Fossils, genes and the evolution of animal limbs

ABSTRACT The morphological and functional evolution of appendages has played a crucial role in the adaptive radiation of tetrapods, arthropods and winged insects. The origin and

diversification of fins, wings and other structures, long a focus of palaeontology, can now be approached through developmental genetics. Modifications of appendage number and architecture

in each phylum are correlated with regulatory changes in specific patterning genes. Although their respective evolutionary histories are unique, vertebrate, insect and other animal

appendages are organized by a similar genetic regulatory system that may have been established in a common ancestor. Access through your institution Buy or subscribe This is a preview of

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AND HOMOLOGY OF ARTHROPOD LIMB BRANCHES Article Open access 30 July 2021 CONVERGENT EVOLUTION IN AFROTHERIA AND NON-AFROTHERIANS DEMONSTRATES HIGH EVOLVABILITY OF THE MAMMALIAN INNER EAR

Article Open access 16 September 2024 KNOCKOUT OF CRUSTACEAN LEG PATTERNING GENES SUGGESTS THAT INSECT WINGS AND BODY WALLS EVOLVED FROM ANCIENT LEG SEGMENTS Article 01 December 2020

REFERENCES * Müller, G. B. & Wagner, G. P. Novelty in evolution: Restructuring the concept. _Ann. Rev. Ecol. Syst._ 22, 229–256 (1991). Article  Google Scholar  * Coates, M. I. The

origin of vertebrate limbs. _Development (suppl.)_ 169–180 (1994). * Coates, M. I. Fish fins or tetrapod limbs—a simple twist of fate? _Curr. Biol._ 5, 844–848 (1995). Article  CAS  PubMed 

Google Scholar  * Shubin, N. The evolution of paired fins and the origin of tetrapod limbs. _Evol. Biol._ 28, 39–85 (1995). Article  Google Scholar  * Coates, M. I. The Devonian tetrapod

_Acanthostega gunnari_ Jarvik: postcranial anatomy, basal tetrapod interrelationships and patterns of skeletal evolution. _Trans. R. Soc. Edinb._ 87, 363–421 (1996). Article  Google Scholar

  * Johnson, R. & Tabin, C. The long and short of _hedgehog_ signaling. _Cell_ 81, 313–316 (1995). Article  CAS  PubMed  Google Scholar  * Nelson, C. E. et al. Analysis of _Hox_ gene

expression in the chick limb bud. _Development_ 122, 1449–1466 (1996). CAS  PubMed  Google Scholar  * Tabin, C. J. & Laufer, E. _Hox_ genes and serial homology. _Nature_ 361, 692–693

(1993). Article  ADS  Google Scholar  * Sordino, P., van der Hoeven, F. & Duboule, D. _Hox_ gene expression in teleost fins and the origin of vertebrate digits. _Nature_ 375, 678–681

(1995). Article  ADS  CAS  PubMed  Google Scholar  * Kessel, M. & Gruss, P. Murine developmental control genes. _Science_ 249, 374–379 (1990). Article  ADS  CAS  PubMed  Google Scholar 

* Mackem, S., Ranson, M. & Mahon, K. Limb-type differences in expression domains of certain chick _Hox_-4 genes and relationship to pattern modification for flight. _Prog. Clin. Biol.

Res._ 383 A, 21–30 (1993). Google Scholar  * Peterson, R. J., Papenbrock, T., Davada, M. M. & Awgulewitschh, A. The murine _Hoxc_ cluster contains five neighboring _abdB_-related Hox

genes that show unique spatially coordinated expression in posterior embryonic subregions. _Mech. Dev._ 47, 253–260 (1994). Article  CAS  PubMed  Google Scholar  * Gibson-Brown, J. J. et al.

Evidence of a role for _T-box_ genes in the evolution of limb morphogenesis and the specification of forelimb/hindlimb identity. _Mech. Dev._ 56, 93–101 (1996). Article  CAS  PubMed  Google

Scholar  * Davis, A. P., Witte, D. P., Hsieh-Li, H. M., Potter, S. S. & Capecchi, M. R. Absence of radius and ulna in mice lacking _hoxa-11_ and _hoxd-11_. _Nature_ 375, 791–795 (1995).

Article  ADS  CAS  PubMed  Google Scholar  * Vorobyeva, E. & Hinchliffe, J. R. From fins to limbs. _Evol. Biol._ 29, 263–311 (1996). Google Scholar  * Hinchliffe, J. R. & Johnson,

D. R. _The Development of the Vertebrate Limb_ (Clarendon, Oxford, 1980). Google Scholar  * Holmgren, N. On the origin of the tetrapod limb. _Acta Zoologica_ 14, 185–295 (1933). Article 

Google Scholar  * Holmgren, N. Contribution on the question of the origin of the tetrapod limb. _Acta Zoologica_ 20, 89–124 (1939). Article  Google Scholar  * Watson, D. M. S. On the

primitive tetrapod limb. _Anat. Anzeiger_ 44, 24–27 (1913). Google Scholar  * Gregory, W. K. & Raven, H. C. Studies on the origin and early evolution of paired fins and limbs. _Ann. N.

Y. Acad. Sci._ 42, 273–360 (1941). Article  ADS  Google Scholar  * Sordino, P. & Duboule, D. Amolecular approach to the evolution of vertebrate paired appendages. _Trends Ecol. Evol._

11, 114–119 (1996). Article  CAS  PubMed  Google Scholar  * Ahlberg, P. E. & Milner, A. R. The origin and early diversification of tetrapods. _Nature_ 368, 507–512 (1994). Article  ADS 

Google Scholar  * Yokouchi, Y. et al. Homeobox gene expression correlated with the bifurcation process of limb cartilage development. _Nature_ 353, 443–445 (1991). Article  ADS  CAS  PubMed

  Google Scholar  * Gerard, M., Duboule, D. & Zakany, J. C. Cooperation of regulatory elements involved in the activation of the _Hoxd-11_ gene. _Compt. R. Acad. Sci. III_ 316, 985–994

(1993). CAS  Google Scholar  * Beckers, J., Gerard, M. & Duboule, D. Transgenic analysis of a potential _Hoxd-11_ limb regulatory element present in tetrapods and fish. _Dev. Biol._ 180,

543–553 (1996). Article  CAS  PubMed  Google Scholar  * van der Hoeven, F., Zakany, J. & Duboule, D. Gene transpositions in the _HoxD_ complex reveal a hierarchy of regulatory controls.

_Cell_ 85, 1025–1035 (1996). Article  CAS  PubMed  Google Scholar  * Shubin, N. & Alberch, P. Amorphogenetic approach to the origin and basic organization of the tetrapod limb. _Evol.

Biol._ 20, 318–390 (1986). Google Scholar  * Tabin, C. J. Why we have (only) five fingers per hand: _hox_ genes and the evolution of paired limbs. _Development_ 116, 289–296 (1992). CAS 

PubMed  Google Scholar  * Holder, N. Developmental constraints and the evolution of vertebrate digit patterns. _J. Theor. Biol._ 104, 451–471 (1983). Article  CAS  PubMed  Google Scholar  *

Morse, E. On the tarsus and carpus of birds. _Ann. Lyc. Nat. Hist._ 10, 141–158 (1872). Article  Google Scholar  * Shubin, N., Crawford, A. & Wake, D. Morphological variation in the

limbs of _Taricha granulosa_ (Caudata: Salamandridae): Evolutionary and phylogenetic implications. _Evolution_ 49, 874–884 (1995). Article  PubMed  Google Scholar  * Greer, A. Limb reduction

in the Scincid lizard genus _Lerista_. 2. Variation in the bone complements of the front and rear limbs and the number of postsacral vertebrae. _J. Herpetol._ 24, 142–150 (1980). Article 

Google Scholar  * Lande, R. Evolutionary mechanisms of limb loss in tetrapods. _Evolution_ 32, 73–92 (1978). Article  PubMed  Google Scholar  * Gauthier, J. Saurischian monophyly and the

origin of birds. _Mem. Calif. Acad. Sci._ 8, 1–55 (1986). Google Scholar  * MacFadden, B. J. _Fossil Horses_ (Cambridge Univ. Press, 1992). Google Scholar  * Davis, A. P. & Capecchi, M.

R. Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of _hoxd-11_. _Development_ 120, 2187–2198 (1994). CAS  PubMed  Google Scholar  * Davis, A. P. &

Capecchi, M. R. Amutational analysis of the 5′ _HoxD_ genes: Dissection of genetic interactions during limb development in the mouse. _Development_ 122, 1175–1185 (1996). CAS  PubMed  Google

Scholar  * Favier, B. et al. Functional cooperation between the non-paralogous genes _Hoxa-10_ and _Hoxd0_-11 in the developing forelimb and axial skeleton. _Development_ 122, 449–460

(1996). CAS  PubMed  Google Scholar  * Dollé, P. et al. Disruption of the _Hoxd_-13 gene induces localized heterochrony leading to mice with neotenic limbs. _Cell_ 75, 431–441 (1993).

Article  PubMed  Google Scholar  * Favier, B., LeMeur, M., Chambon, P. & Dollé, P. Axial skeleton homeosis and forelimb malformations in _Hoxd_-11 mutant mice. _Proc. Natl Acad. Sci.

USA_ 92, 310–314 (1995). Article  ADS  CAS  PubMed  PubMed Central  Google Scholar  * Capecchi, M. R. Function of homeobox genes in skeletal development. _Ann. N. Y. Acad. Sci._ 97, 34–37

(1996). Article  ADS  Google Scholar  * Wigglesworth, V. B. Evolution of insect wings and flight. _Nature_ 246, 127–203 (1973). Article  ADS  Google Scholar  * Budd, G. The morphology of

_Opabinia regalis_ and the reconstruction of the arthropod stem-group. _Lethaia_ 29, 1–14 (1996). Article  Google Scholar  * Hou, X. G. & Bergström, J. Cambrian lobopodians—ancestors of

extant onychophorans? _Zool. J. Linn. Soc. Lond._ 114, 3–19 (1995). Article  Google Scholar  * Simonetta, A. M. & Delle Cave, L. in _The Early Evolution of Metazoa and the Significance

of Problematic Taxa_ (eds Simonetta, A. M. & Conway Morris, S.) 189–244 (Cambridge Univ. Press, 1991). Google Scholar  * Budd, G. ACambrian gilled lobopod from Greenland. _Nature_ 364,

709–711 (1993). Article  ADS  Google Scholar  * Chen, J. Y., Ramsköld, L. & Zhou, G. Q. Evidence for monophyly and arthropod affinity of Cambrian giant predators. _Science_ 264,

1304–1308 (1994). Article  ADS  CAS  PubMed  Google Scholar  * Carroll, S. B. Homeotic genes and the evolution of arthropods and chordates _Nature_ 376, 479–485 (1995). Article  ADS  CAS 

PubMed  Google Scholar  * Struhl, G. Genes controlling segmental specification in the _Drosophila_ thorax. _Proc. Natl Acad. Sci. USA_ 79, 7380–7384 (1982). Article  ADS  CAS  PubMed  PubMed

Central  Google Scholar  * Struhl, G. Ahomoeotic mutation transforming leg to antenna in _Drosophila_. _Nature_ 292, 635–638 (1981). Article  ADS  CAS  PubMed  Google Scholar  * Gibson, G.

& Gehring, W. J. Head and thoracic transformations caused by ectopic expression of _Antennapedia_ during _Drosophila_ development. _Development_ 102, 657–675 (1988). Google Scholar  *

Stuart, J., Brown, S., Beeman, R. & Denell, R. Adeficiency of the homeotic complex of the beetle _Tribolium_. _Nature_ 350, 72–47 (1991). Article  ADS  CAS  PubMed  Google Scholar  *

Averof, M. & Akam, M. _Hox_ genes and the diversification of insect–crustacean body plans. _Nature_ 376, 420–423 (1995). Article  ADS  CAS  PubMed  Google Scholar  * Vachon, G. et al.

Homeotic genes of the Bithorax complex repress limb development in the abdomen of the _Drosophila_ embryo through the target gene. _Cell_ 71, 437–450 (1992). Article  CAS  PubMed  Google

Scholar  * Panganiban, G. et al. The development of crustacean limbs and the evolution of arthropods. _Science_ 270, 1363–1366 (1995). Article  ADS  CAS  PubMed  Google Scholar  * Manton, S.

M. _Mandibular Mechanisms and the Evolution of Arthropods_ VOL. 247 (British Museum and Queen Mary College, London, 1964). Google Scholar  * Wheeler, W. C., Cartwright, P. & Hayashi, C.

Y. Arthropod phylogeny: a combined approach. _Cladistics_ 9, 1–39 (1993). Article  PubMed  Google Scholar  * Boore, J. L., Collins, T. M., Stanton, D., Daehler, L. L. & Brown, W. M.

Deducing the pattern of arthropod phylogeny from mitochondrial DNA rearrangements. _Nature_ 376, 163–165 (1995). Article  ADS  CAS  PubMed  Google Scholar  * Cohen, S. M. & Jürgens, G.

Proximal–distal pattern formation in _Drosophila_: cell autonomous requirement for _Distal-less_ gene activity in limb development. _EMBO J._ 8, 2045–2055 (1989). Article  CAS  PubMed 

PubMed Central  Google Scholar  * Cohen, S. et al. _Distal-less_ encodes a homeodomain protein required for limb development in _Drosophila_. _Nature_ 338, 432–434 (1989). Article  ADS  CAS

  PubMed  Google Scholar  * Panganiban, G., Nagy, L. & Carroll, S. B. The development and evolution of insect limb types. _Curr. Biol._ 4, 671–675 (1994). Article  CAS  PubMed  Google

Scholar  * Popadic, A., Rusch, D., Peterson, M., Rogers, B. T. & Kaufman, T. C. Origin of the arthropod mandible. _Nature_ 380, 395 (1996). Article  ADS  CAS  Google Scholar  * Jeram, A.

J., Selden, P. A. & Edwards, D. Land animals in the Silurian: Arachinids and myriapods from Shropshire, England. _Science_ 250, 658–661 (1990). Article  ADS  CAS  PubMed  Google Scholar

  * Kukalová-Peck, J. _The Insects of Australia 2nd edn_ (Cornell University Press, Ithaca, NY, 1991). Google Scholar  * Snodgrass, R. _Principles of Insect Morphology_ (McGraw-Hill, New

York, 1935). Google Scholar  * . Kukalova-Peck, J. Origin and evolution of insect wings and their relation to metamorphosis, as documented from the fossil record. _J. Morphol._ 156, 53–126

(1978). Article  PubMed  Google Scholar  * Marden, J. H. & Kramer, M. G. Surface-skimming stoneflies: A possible intermediate stage in insect flight evolution. _Science_ 266, 427–430

(1994). Article  ADS  CAS  PubMed  Google Scholar  * Cohen, B. et al. Allocation of the thoracic imaginal primordia in the Drosophila embryo. _Development_ 117, 597–608 (1993). CAS  PubMed 

Google Scholar  * Diaz-Benjumea, F. & Cohen, S. M. Interaction between dorsal and ventral cells in the imaginal disc directs wing development in _Drosophila_. _Cell_ 75, 741–752 (1993).

Article  CAS  PubMed  Google Scholar  * Carroll, S. B. et al. Pattern formation and eyespot determination in butterfly wings. _Science_ 265, 109–114 (1994). Article  ADS  CAS  PubMed  Google

Scholar  * Averof, M. & Cohen, S. M. Evolutionary origin of insect wings from ancestral gills. _Nature_ 385, 627–630 (1997). Article  ADS  CAS  PubMed  Google Scholar  * Lee, J. J. et

al. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene _hedgehog_. _Cell_ 71, 33–50 (1992). Article  CAS  PubMed  Google

Scholar  * Tabata, T. et al. The _Drosophila hedgehog_ gene is expressed specifically in posterior compartment cells and is a target of _engrailed_ regulation. _Genes Dev._ 6, 2635–2645

(1992). Article  CAS  PubMed  Google Scholar  * Basler, D. & Struhl, G. Compartment boundaries and the control of _Drosophila_ limb pattern by _hedgehog_ protein. _Nature_ 368, 208–214

(1994). Article  ADS  CAS  PubMed  Google Scholar  * Posakony, L., Raftery, L. & Gelbart, W. Wing formation in _Drosophila melanogaster_ requires _decapentaplegic_ gene function along

the anterior–posterior compartment boundary. _Mech. Dev._ 33, 69–82 (1991). Article  Google Scholar  * Capdevila, J. & Guerrero, I. The _Drosophila_ segment polarity gene _patched_

interacts with _decapentaplegic_ in wing development. _EMBO J._ 6, 715–729 (1994). Google Scholar  * Sanicola, M., Sekelsky, J., Elson, S. & Gelbart, W. M. Drawing a stripe in

_Drosophila_ imaginal discs: negative regulation of _decapentaplegic_ and _patched_ expression. _Genetics_ 139, 745–756 (1995). CAS  PubMed  PubMed Central  Google Scholar  * Nellen, D.,

Burke, R., Struhl, G. & Basler, K. Direct and long-range actions of a _Dpp_ morphogen gradient. _Cell_ 85, 357–368 (1996). Article  CAS  PubMed  Google Scholar  * Lecuit, T. et al. Two

distinct mechanisms for long-range patterning by _Decapentaplegic_ in the _Drosophila_ wing. _Nature_ 381, 387–393 (1996). Article  ADS  CAS  PubMed  Google Scholar  * Echelard, Y. et al.

_Sonic hedgehog_, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. _Cell_ 75, 1417–1430 (1993). Article  CAS  PubMed  Google Scholar  *

Krauss, S., Concordet, J. P. & Ingham, P. W. Afunctionally conserved homolog of the _Drosophila_ segment polarity gene _hh_ is expressed in tissues with polarizing activity in zebrafish

embryos. _Cell_ 75, 1431–1444 (1993). Article  CAS  PubMed  Google Scholar  * Chang, D. T. et al. Products, genetic linkage and limb patterning activity of a murine _hedgehog_ gene.

_Development_ 120, 3339–3353 (1994). CAS  PubMed  Google Scholar  * Riddle, R. D. et al. _Sonic hedgehog_ mediates the polarizing activity of the ZPA. _Cell_ 75, 1401–1416 (1995). Article 

Google Scholar  * Tickle, C. Genetics and limb development. _Dev. Genet._ 19, 1–8 (1996). Article  CAS  PubMed  Google Scholar  * Irvine, K. & Weischaus, E. _fringe_, a boundary-specific

signaling molecule, mediates interactions between dorsal and ventral cells during _Drosophila_ wing development. _Cell_ 79, 595–606 (1994). Article  CAS  PubMed  Google Scholar  *

Spreicher, S., Thomas, U., Hinz, U. & Knust, E. The _Serrate_ locus of _Drosophila_ and its role in morphogenesis or imaginal discs: control of cell proliferation. _Development_ 120,

535–544 (1994). Google Scholar  * Kim, J., Irvine, K. & Carroll, S. Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing

_Drosophila_ wing. _Cell_ 82, 795–802 (1995). Article  CAS  PubMed  Google Scholar  * Couso, J. P., Knust, E. & Martinez Ariias, A. _Serrate_ and _wingless_ cooperate to induce

_vestigial_ gene expression and wing formation in _Drosophila_. _Curr. Biol._ 5, 1437–1448 (1995). Article  CAS  PubMed  Google Scholar  * Diaz-Benjumea, F. J. & Cohen, S. _Serrate_

signals through _Notch_ to establish a _Wingless_-dependent organizer at the dorsal/ventral compartment boundary of the _Drosophila_ wing. _Development_ 121, 4215–4225 (1995). CAS  PubMed 

Google Scholar  * Kim, J. et al. Integration of positional signals and regulation of wing formation and identity by _Drosophila vestigial_ gene. _Nature_ 382, 133–138 (1996). Article  ADS 

CAS  PubMed  Google Scholar  * Todt, W. L. & Fallon, J. F. Development of the apical ectodermal ridge in the chick wing bud. _J. Embryol. Exp. Morphol._ 80, 21–41 (1984). CAS  PubMed 

Google Scholar  * Rodriguez-Estaban, C. et al. _Radical fringe_ positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb. _Nature_ 386, 360–361 (1997).

Article  ADS  Google Scholar  * Laufer, E. et al. Expression of _Radical fringe_ in limb-bud ectoderm regulates apical ectodermal ridge formation. _Nature_ 386, 366–373 (1997). Article  ADS

  CAS  PubMed  Google Scholar  * Williams, J. A., Paddock, S. W. & Carroll, S. B. Pattern formation in a secondary field: A hierarchy of regulatory genes subdivides the developing

_Drosophila_ wing disc into discrete sub-regions. _Development_ 117, 571–584 (1993). CAS  PubMed  Google Scholar  * Couso, J. P., Bate, M. & Martinez-Ariias, A. A_wingless_-dependent

polar coordinate system in _Drosophila_ imaginal discs. _Science_ 259, 484–489 (1993). Article  ADS  CAS  PubMed  Google Scholar  * Parr, B. A. & McMahon, A. P. Dorsalizing signal

_Wnt-7a_ required for normal polarity of D-V and A-P axes of mouse limb. _Nature_ 374, 350–353 (1995). Article  ADS  CAS  PubMed  Google Scholar  * Riddle, R. D. et al. Induction of the LIM

homeobox gene _Lmx-1_ by _Wnt-7a_ establishes dorsoventral pattern in the vertebrate limb. _Cell_ 83, 631–640 (1995). Article  CAS  PubMed  Google Scholar  * Vogel, A. et al. Dorsal cell

fate specified by chick _Lmx1_ during vertebrate limb development. _Nature_ 378, 716–720 (1995). Article  ADS  CAS  PubMed  Google Scholar  * Raff, R. _The Shape of Life_ (Univ. Chicago

Press, 1996). Book  MATH  Google Scholar  * Panganiban, G. et al. The origin and evolution of animal appendages. _Proc. Natl Acad. Sci. USA_ 94, 5162–5166 (1997). Article  ADS  CAS  PubMed 

PubMed Central  Google Scholar  * Wall, N. A. & Hogan, B. L. M. Expression of _bone morphogenetic protein_-4 (_BMP_-4), _bone morphogenetic protein-7_ (_BMP-7_), _fibroblast growth

factor_-8 (_FGF_-8) and _Sonic hedgehog_ (_SHH_) during branchial arch development in the chick. _Mech. Dev._ 53, 383–392 (1995). Article  CAS  PubMed  Google Scholar  * Marigo, V., Scott,

M. P., Johnson, R. L., Goodrich, L. V. & Tabin, C. J. Conservation in _hedgehog_ signaling: induction of a chicken _patched_ homolog by _Sonic hedgehog_ in the developing limb.

_Development_ 122, 1225–1233 (1996). CAS  PubMed  Google Scholar  * Roth, V. L. Homology and hierarchies: Problems solved and unresolved. _J. Evol. Biol._ 4, 167–194 (1991). Article  Google

Scholar  * Wagner, G. P. The origin of morphological characters and the biological basis of homology. _Evolution_ 43, 1157–1171 (1989). Article  CAS  PubMed  Google Scholar  * Bolker, J. A.

& Raff, R. A. Developmental genetics and traditional homology. _BioEssays_ 18, 489–494 (1996). Article  CAS  PubMed  Google Scholar  * Carroll, R. L. _Vertebrate Paleontology_ (Freeman,

San Francisco, 1988). Google Scholar  * Jarvik, E. _The Structure and Evolution of the Vertebrates_ VOL. 1 (Academic, New York, 1980). Google Scholar  * Jarvik, E. The Devonian tetrapod

_Ichthyostega_. _Fossils and Strata_ 40, 1–213 (1996). Google Scholar  * Fromental-Ramain, C. et al. Specific and redundant functions of the paralogous _Hoxa-_9 and _Hoxd-_9 genes in

forelimb and axial skeleton patterning. _Development_ 122, 461–472 (1996). CAS  PubMed  Google Scholar  * Mortlock, D. P., Post, L. C. & Innis, J. W. The molecular basis of hypodactyly

(Hd): a deletion in _Hoxa13_ leads to arrest of digital arch formation. _Nature Genet._ 13, 284–289 (1996). Article  CAS  PubMed  Google Scholar  * Mortlock, D. P. & Innis, J. W.

Mutation of _HOXA13_ in hand–foot–genital syndrome. _Nature Genet._ 15, 179–181 (1997). Article  CAS  PubMed  Google Scholar  * Saunders, J. The proximo-distal sequence of origin of the

parts of the chick wing and the role of the ectoderm. _J. Exp. Zool._ 108, 363–403 (1948). Article  PubMed  Google Scholar  * Summerbell, D., Lewis, J. H. & Wolpert, L. Postional

information in chick limb morphogenesis. _Nature_ 244, 492–496 (1973). Article  ADS  CAS  PubMed  Google Scholar  * Lebedev, O. A. & Coates, M. I. The postcranial skeleton of the

Devonian tetrapod _Tulerpeton curtum_ Lebedev. _Zool. J. Linn. Soc._ 113, 302–348 (1995). Google Scholar  * Hou, X. G., Bergström, J. & Ahlberg, P. _Anomalocaris_ and other large animals

in the Lower Cambrian Chenjiang fauna of southwest China. _Geol Forening. Forhandling._ 117, 163–183 (1995). Google Scholar  Download references ACKNOWLEDGEMENTS We thank P. Ahlberg, G.

Budd, A. C. Burke, M. Coates, A. Meyer, G. Panganiban, P. Sniegowski, D. Wake, R. S. Winters, L. Wolpert and members of our laboratories for their critiques of drafts of this manuscript.

S.B.C. is an investigator of the HHMI. C.T. is supported by grants from the NIH and the American Cancer Society. N.S. is supported by grants from the NSF, from the National Geographic

Society and from the Research Foundation of the University of Pennsylvania. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biology, University of Pennsylvania, Philadelphia,

19104, Pennsylvania, USA Neil Shubin * Cliff Tabin is in the Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA Cliff Tabin * Sean Carroll

is at the HHMI and Laboratory of Molecular Biology, University of Wisconsin, 1525 Linden Drive, Madison, 53706, Wisconsin, USA Sean Carroll * Correspondence and requests for materials

should be addressed to N.S., Neil Shubin Authors * Neil Shubin View author publications You can also search for this author inPubMed Google Scholar * Cliff Tabin View author publications You

can also search for this author inPubMed Google Scholar * Sean Carroll View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR

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