Anthony Graham

The pectoral girdle evolved inprimitive fish as a support for thepectoral fins, and wasjuxtaposed to the base of theskull. During subsequentevolution, however, therelationship between the pectoralgirdle and the skull hasundergone substantialmodifications [1,2]. With theemergence of the tetrapods thepectoral girdle lost itsattachment to the skull, and wasthen subsequently displacedposteriorly as a number of

cervical vertebrae were insertedbetween the pectoral girdle andthe skull, forming a true neck.These modifications facilitatedthe colonisation of the land bytetrapods as they allowed themovement of the headindependently of the limbs.

Although there have beenalterations to the relationshipbetween the pectoral girdle andthe skull, and indeed to theskeletal components of thepectoral girdle, the muscleattachments between thepectoral girdle and the skull areremarkably conserved amongst

the vertebrates. Thus, with theevolution of a neck in tetrapodsthere had to be put in placemechanisms that would allowmuscle connectivity to beorganised between the head andthe trunk. This is particularlyintriguing because the head andthe trunk differ with respect tothe embryonic tissues that areemployed to organiseskeletomuscular connectivity. Inthe head, it is the neural crestcells that fulfills this role [3],whilst in the trunk it is themesoderm [4].

A recent study [5] employinggenetic labelling in mice has nowuncovered the developmentalbasis of the systems that act topattern the muscle connectivitybetween the pectoral girdle andthe skull. Importantly, this workhas revealed the existence ofcryptic boundaries within theneck and pectoral girdle(Figure 1). Muscles linking thehead to the pectoral girdle, the

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integration that apply so well inthe colliculi can be applied tomultisensory phenomena at thelevel of perception, behaviour, oreven in different multisensorybrain areas, at least for thosebehaviours not involvingorienting movements. A well-known and striking example ofmultisensory integration, theMcGurk illusion [20], isunaffected by the relativelocations of visual and auditoryspeech signals [11]. Thisexample violates the spatial rule,and suggests that it musttherefore depend on qualitativelydifferent principles ofmultisensory integration, mostlikely implemented in brain areasfar removed from the superiorcolliculi. Uncovering theprinciples and mechanisms ofmultisensory integration both inthe colliculi and in the brainbeyond the midbrain represent afascinating research prospect,for humans and felines alike.

References1. Critchley, M. (1966). The divine banquet

of the brain. (London, Harrison & Sons).2. Horn, G., and Hill, R.M. (1964).

Habituation of the response to sensory

stimuli of neurones in the brain stem ofrabbits. Nature 202, 296–298.

3. Stein, B.E., Magalhães-Castro, B., andKruger, L. (1975). Superior colliculus:Visuotopic-somatotopic overlap. Science189, 224–226.

4. Hartline, P.H., Kass, L., and Loop, M.S.(1978). Merging of modalities in the optictectum: Infrared and visual integration inrattlesnakes. Science 199, 1225–1228.

5. Knudsen, E.I. (1982). Auditory and visualmaps of space in the optic tectum of theowl. J. Neurosci. 2, 1177–1194.

6. Meredith, M.A., and Stein, B.E. (1983).Interactions among converging sensoryinputs in the superior colliculus. Science221, 389–391.

7. King, A.J., and Palmer, A.R. (1985).Integration of visual and auditoryinformation in bimodal neurones in theguinea-pig superior colliculus. Exp. BrainRes. 60, 492–500.

8. Bodznick, D. (1990). Elasmobranchvision: multimodal integration in thebrain. J. Exp. Zool. Suppl. 5, 108–116.

9. Stanford, T.R., Quessy, S., and Stein,B.E. (2005). Evaluating the operationsunderlying multisensory integration inthe cat superior colliculus. J. Neurosci.25, 6499–6508.

10. Spence, C., and Driver, J. (1997).Audiovisual links in exogenous covertspatial orienting. Percept. Psychophys.59, 1–22.

11. Spence, C., and Driver, J. (2004).Crossmodal space and crossmodalattention. (Oxford, Oxford UniversityPress).

12. Stein, B.E., Meredith, M.A., Huneycutt,W.S., and McDade, L. (1989). Behavioralindices of multisensory integration:Orientation to visual cues is affected byauditory stimuli. J. Cogn. Neurosci. 1,12–24.

13. Bolognini, N., Rasi, F., and Ladavas, E.(2005). Visual localization of sounds.

Neuropsychologia 43, 1655–1661.14. Calvert, G.A., Hansen, P.C., Iversen,

S.D., and Brammer, M.J. (2001).Detection of audio-visual integrationsites in humans by application ofelectrophysiological criteria to the BOLDeffect. Neuroimage 14, 427–438.

15. Knudsen, E.I., and Brainard, M.S. (1991).Visual instruction of the neural map ofauditory space in the developing optictectum. Science 253, 85–87.

16. Wallace, M.T., Perrault, T.J. Jr., Hairston,W.D., and Stein, B.E. (2004). Visualexperience is necessary for thedevelopment of multisensory integration.J. Neurosci. 24, 9580–9584.

17. Skaliora, I., Doubell, T.P., Holmes, N.P.,Nodal, F.R., and King, A.J. (2004).Functional topography of convergingvisual and auditory inputs to neurones inthe rat superior colliculus. J.Neurophysiol. 92, 2933–2946.

18. Meredith, M.A., Nemitz, J.W., and Stein,B.E. (1987). Determinants ofmultisensory integration in superiorcolliculus neurons. I. Temporal factors. J.Neurosci. 7, 3215–3229.

19. Stein, B.E., Wallace, M.W., Stanford,T.R., and Jiang, W. (2002). Cortexgoverns multisensory interactions in themidbrain. Neuroscientist 8, 306–314.

20. McGurk, H., and MacDonald, J. (1976).Hearing lips and seeing voices. Nature264, 746–748.

Department of ExperimentalPsychology, University of Oxford,Oxford OX1 3UD, UK.E-mail:nicholas.p.holmes@wolfson.oxon.ac.orgcharles.spence@psy.ox.ac.uk

DOI: 10.1016/j.cub.2005.08.058

Vertebrate Evolution: TurningHeads

The skeleton of the neck and shoulders has undergone alterationsduring evolution, but muscle connectivity has not. A recent studysuggests this is a result of neural crest cells defining attachmentpoints and thus muscle connectivity.

shoulder girdle and clavicle, areorganised by neural crest cells,while trunk muscles attaching tothe pectoral girdle are organisedby mesodermal cells. Theseresults are important, as theyprovide insights into how theskeletal components of the neckhave been altered duringevolution without disturbing themuscle scaffolds. They are alsoof significance as they helpexplain the aetiological basis of anumber of human syndromeswhich present particularmalformations of the neck andshoulder.

The role of the neural crest andthe mesoderm in organising theconnectivity of the neck muscleswas previously unresolved. Todetermine the roles of these twoembryonic populations in thisregion of the body, Matsuoka etal. [5] used genetic strategies topermanently label the neuralcrest or the mesoderm. To labelthe neural crest, they used amouse line carrying the wnt-1enhancer to drive expression ofCre recombinase in thepremigatory neural crest, andadditionally another lineemplyoing the regulatoryelements of Sox-10 to expressCre recombinase in migratingneural crest cells.

These mice were then crossedwith reporter lines carrying LacZor GFP cassettes, which have astop signal placed upstream. Inthe offspring of these crosses theLacZ or GFP reporters areswitched on in those cellsexpressing Cre recombinase, asthis directs the removal of thestop signal in front of thesecassettes. Cre recombinasemediates a specific alteration tothe DNA of the cells that expressit, so this alteration is inheritedby all of the neural crest and allof its progeny.

To label the mesoderm, theyused a different transgenicstrategy but one that againemployed Cre recombinase tomodify the DNA of the cells thatexpress this enzyme, and theirprogeny, resulting in theexpression of the LacZ reporter.To specifically label themesoderm, they used regulatoryelements from the HoxD4 gene,

which drive expression in trunksomites and neural tube but notin the neural crest.

An important result thatemerged from the neural crestlabelling studies was that thisembryonic population has anextensive contribution to theneck region, and that these cellsform skeletal and muscleconnective tissue cells. Theneural crest derivatives werefound to occupy two domains,one external and another lyingventrally and internal. The cells ofthe external domains form,amongst other things, theconnective tissue and theattachment points of the largetrapezius muscle, which arelocated at the occipitalprotuberance at the back of thehead and the anterior of theshoulder girdle.

The crest cells that occupy themore ventral position generatethe connective tissues and theattachment points of thesterno-cleido-mastoid muscles,which are found on the mastoidprocess of the skull and theanterior of the clavicle andsternum. This ventral crestpopulation also forms theconnective tissue and attachmentpoints of the muscles involved inswallowing.

Interestingly, it was found thatthere is no relationship betweenattachment points formed by theneural crest and their mode ofossification, endochondral ordermal. The cells that form theattachment point of the trapeziuson the shoulder girdle areendochondral, whilst in theclavicle neural crest cells formboth enodchondral bone, as wellgenerating the anterior dermalossification centre.

The mesodermal fate map alsorevealed surprising results. It was

found that trunk and limbmuscles that attach to thepectoral girdle, such as thepectoral and deltoid, havemesodermally derivedattachment points. Thus, headand trunk muscles that attachto the pectoral girdle differ inthe embryonic origin of the cellsthat form their attachmentpoints; head muscle attach toneural crest derived attachmentpoint, trunk muscles tomesoderm derived attachmentpoints. Another interestingobservation that emerged wasthat that the posterior dermalossification of the clavicle has amesodermal origin, which refutedprevious studies suggesting thatany dermal bones in the trunkwere likely to be neural crestderived.

During tetrapod evolution, thecomposition of the pectoral girdlehas undergone major changes[1,2]. There has been a change inthe relative contribution ofdermal versus endochondralbones. One particular skeletalelement that has been alteredduring tetrapod evolution is thecleithrum. This dermal bone isthe central most shoulder bone ofall bony fish, which is absentfrom all living tetrapods exceptfrogs. In bony fish, the cleithrumserves as the attachment for thetrapezius/cucullaris muscleanteriorly and for trunk musclesposteriorly.

Although mammals lack acleithrum, however, there hasbeen no alteration in the patternof muscle attachment, and inthese animals the scapular spineis positioned between thetrapezius and trunk muscleattachment systems. Theconservation of neck muscleattachments in the face of suchalterations is explained by the

Dispatch R765

Figure 1. Diagram of anadult mouse head, neckand pectoral girdle,showing the contribution ofthe neural crest (in red) andthe mesoderm (in blue) tothe skeletal and connectivetissues.

David A. Leopold and Melanie Wilke

“But what has really been learnedby functional imaging?” Whisperedquips such as this were oftenoverheard in past years atneuroscience meetings amid rowsof colorful posters. Spatial maps ofbrain activity were initially met withskepticism by electrophysiologistswho, while perhaps ready toconcede defeat in the aesthetics ofdata presentation, claimed toprefer their more serious science.Yet in the past years, functionalmagnetic resonance imaging(fMRI) has moved forward at anenviable pace, and many of the

initial skeptics are now themselvesensnared in its details.

As in many fields of science,descriptions of the brain arisefrom, and are ultimately shapedby, contemporary technology. Invisual neurophysiology, thepredominance of single unitrecordings during the last decadeshas provided concepts such asfeature selectivity and receptivefield structure, which now serve asthe building blocks for theories ofhow we see. These concepts are,nonetheless, strongly linked to aparticular experimental paradigm,and may therefore be limited intheir capacity to support a generaltheory of visual processing. This

issue becomes apparent whentrying to understand fMRI datausing conceptual frameworksoriginally derived from single unitrecordings. In fMRI, voxels are thefundamental spatial unit ofmeasurement. Unlike singleneurons, a voxel is a volumetricentity that does not map directlyonto any particular functionalquantity. Instead, each containsthousands to millions of neurons,whose collective activity is usuallymeasured indirectly through itsimpact on the vasculature. Butalong with these potentiallyundesirable aspects of fMRI is thegreat advantage of being able tomonitor many thousands of voxelsat once, throughout the entirebrain.

But how is it possible to keeptrack of thousands ofsimultaneously measured signals?From the start of functionalimaging, the answer has been tocreate activity maps. In thesemaps, each voxel is typicallyanalyzed independently from the

fact that it is not defined bymodes of ossification, but by theembryonic cell populations thatform the attachment points. Aconclusion that can therefore bedrawn is that the endochondralscapular spine of mammals is theghost of the cleithrum [5].

The discovery of the importantcontribution of the neural crest tothe structures of the neck andshoulder has also allowed anexplanation the aetilogy of somepoorly understood humansyndromes [5]. These includeKlippel-Feil disease, Sprengel’sdeformity, cleidocranialdysplasia, Arnold-Chiari I/IImalformation and ‘cri-du-chat’syndrome, all of which presentdysmorphologies of the neuralcrest derived structures of theneck and shoulder andswallowing problems. It can nowthus be appreciated that thesesyndromes are united by acommon cellular aetiology.

This elegant new study [5]obviously raises questions as tohow the neural crest contributionto the neck is organised. It is

currently unclear from which axiallevel of the developing neuraltubes these neural crest cellsarise. The regulatory elementsused in this study will result inmost neural crest cells beinglabelled. The path of migration ofthese neural crest to the region ofthe developing pectoral girdle isalso unclear. These areinteresting issues theinvestigation of which shouldshed further light on themechanisms that act to order theconnectivity of attachment of theneck muscles. It is probable,based on a previous study inchick [6], that these cells willarise from caudal hindbrain,migrate out between the oticvesicle and the anterior somiteand then track posteriorly alongthe base of the somites. It would,however, given the power of thesingle cell fate mapping that canbe achieved using transgenicmice and the advantages ofmouse genetics, be of greatworth if regulatory elementscould be identified which wouldallow the mapping of crest cells

specifically from the caudalhindbrain.

References1. Kardong, K.V. (1998). Vertebrates,

Comparative Anatomy, Function,Evolution, second edition (New York:WCB McGraw Hill).

2. McGonnell, I.M. (2001). The evolution ofthe pectoral girdle. J. Anat. 199,189–194.

3. Kontges, G., and Lumsden, A. (1996).Rhombencephalic neural crestsegmentation is preserved throughoutcraniofacial ontogeny. Development 122,3229–3242.

4. Chevallier, A., and Kieny, M. (1982). Onthe role of connective tissue in thepatterning of the chick limb musculature.Wilhelm Roux Arch. Dev. Biol. 191,277–280.

5. Matsuoka, T., Ahlberg, P.E., Kessaris, N.,Iannarelli, P., Dennehy, U., Richardson,W.D., McMahon, A.P., and Koentges, G.(2005). Neural crest origins of the neckand shoulder. Nature 436, 347–355.

6. McGonnell, I.M., McKay, I.J., andGraham, A. (2001). A population ofcaudally migrating cranial neural crestcells: functional and evolutionaryimplications. Dev. Biol. 236, 354–363.

MRC Centre for DevelopmentalNeurobiology, King’s College, LondonSE1 1UL, UKE-mail: anthony.graham@kcl.ac.uk

DOI: 10.1016/j.cub.2005.08.060

Current Biology Vol 15 No 18R766

Neuroimaging: Seeing the Treesfor the Forest

New functional imaging studies demonstrate that it is possible todecode a sensory visual pattern, and even an internal perceptual state,by combining seemingly insignificant feature selective signal biasespresent in a large number of voxels.