EVIDENCE OF A ROLE FOR T-BOX GENES IN THE EVOLUTION OF LIMB MORPHOGENESIS AND THE SPECIFICATION OF FORELIMB HINDLIMB IDENTITY/

Tetrapod fore- and hindlimbs have evolved from the pectoral and pelvic fins of an ancient vertebrate ancestor. In this ancestor, the pectora l fin appears to have arisen following the rostral homeotic recapitula tion of an existing pelvic appendage (Tabin and Laufer (1993), Nature 361, 692-693). Thus the basic appendage outgrowth program is reiterate d in both tetrapod fore- and hindlimbs and the pectoral and pelvic fin s of extant teleost fishes (Sordino et al. (1995) Nature 375, 678-681) . Recently a novel family of putative transcription factors, which inc ludes the T (Brachyury) locus, has been identified and dubbed the 'T-b ox' family. In mice, all of these genes have expression patterns indic ative of involvement in embryonic induction (Chapman et al. (1996) Dev . Dyn., in press), and four (Tbx2-Tbx5) are represented as two cognate , linked gene pairs (Agulnik et al., (1996), Genetics, in press). We n ow report that, whereas Tbx2 and Tbx3 are expressed in similar spatiot emporal patterns in both limbs, Tbx5 and Tbx4 expression is primarily restricted to the developing fore- and hindlimb buds, respectively. Th ese observations suggest that T-box genes have played a role in the ev olution of fin and limb morphogenesis, and that Tbx5 and Tbx4 may have been divergently selected to play a role in the differential specific ation of fore- (pectoral) versus hind- (pelvic) limb (fin) identity.