Sonic signals somites Sonic hedgehog, a secreted signalling molecule known to play a role in the patterning of the central nervous system and the limb in vertebrates, also controls differentiation of the somites.

Although it has been known for decades that axial mid-line structures, such as the notochord and neural tube,influence patterning of the nearby paraxial mesoderm invertebrates [1], the mechanisms underlying this phenom-enon have remained obscure. Recent studies by twogroups [2,3] have shed considerable light on this issue.They have demonstrated a role for the secreted protein,Sonic hedgehog, which is synthesized in the notochordand floor plate, in the determination of cell fate duringsomite differentiation. Previous work has established rolesfor Sonic hedgehog in dorsal-ventral patterning of thecentral nervous system and in anterior-posterior specifi-cation in the limb (reviewed in [4]). Now, the develop-mental repertoire of this factor is expanded to includedetermination of the paraxial mesoderm.During vertebrate embryogenesis, the segmental platemesoderm that lies adjacent to the neural tube in thetrunk and tail becomes segmented into paired epithelialsomites. Each transient somite then differentiates intothe ventral sclerotome, from which the skeletal elementsof the ribs and vertebral column derive, and the dorsaldermomyotome. The dermomyotome further differen-tiates into the dorsal-lateral dermotome, which gives riseto dermis, and the myotome, sandwiched between thesclerotome and the dermotome, which gives rise to theaxial musculature (see Fig. 1).Tissue transplantation experiments, primarily with chickembryos, have demonstrated that the development ofthe somites is controlled by axial structures [5]. Specifi-cally, grafts of notochord or floor plate, placed dorsally,lead to suppression of dermomyotome development withconcomitant expansion of the sclerotome. Conversely,Fig. 1. Expression patterns of markers during early developmentof the somites.removal of the notochord leads to a lack of sclerotomedevelopment, as do mouse mutations that interfere withnotochord formation [6]. To ask whether Sonic hedge-hog might mediate the effects of the notochord and floorplate on somite development, Johnson et al. [2] and Fanand Tessier-Lavigne [3] took distinct but complementaryapproaches. Both groups concluded that Sonic hedgehogindeed plays a major role in inducing the formation ofthe sclerotome ventrally while preventing dermomyo-tome formation in this region. In addition, Johnson et al.[2] suggest a role for Sonic hedgehog in the developmentof the myotome.In the chick, Sonic hedgehog is first expressed in Hen-sen's node (a putative organizing center) prior to forma-tion of the first somite, and it continues to be expressedin the notochord and floor plate throughout somitogen-esis, which proceeds by the condensation of successivesomites in a caudal direction. Somites and presomiticmesoderm are therefore continuously exposed to a ven-tral source of Sonic hedgehog. To determine what rolethis factor might play in somite patterning in vivo, John-son et. al. [2] ectopically expressed Sonic hedgehog in thedorsal segmental plate by infection with a retrovirusengineered to express the sonic hedgehog gene. Two daysafter infection, embryos were analyzed with molecularmarkers diagnostic for different somitic regions.One such marker, the transcription factor-encoding genepax-i, is first expressed in chick somites ventral-mediallyin the fourth most recently formed somite, at the timewhen dorsal-ventral pattern becomes irreversibly speci-fied. As the cells in this region delaminate to form thesclerotome, pax-1 expression intensifies and spreads lat-erally, forming a sharp border with the still-epithelialdermomyotome; pax- is therefore a specific marker forsclerotomal cells and their precursors. Embryos injectedwith the Sonic-hedgehog-encoding virus show a dorsalexpansion of the pax- I expression domain on the infec-ted side. Thus, Sonic hedgehog may either reprogramdorsal cells to adopt a sclerotomal fate or increase prolif-eration specifically within the sclerotome, so expandingthe pax- 1-expressing population.To determine whether reprogramming had indeed takenplace, the expression of pax-3 was assessed. This factor isnormally expressed at a low level throughout the chicksegmental plate, but is restricted to the dermomyotomeand finally the dermotome as somite development pro-ceeds. Ectopic expression of sonic hedgehog in the dorsal612 © Current Biology 1995, Vol 5 No 6