Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling.
Despite extensive studies on the anterior-posterior (AP) axis formation of limb buds, mechanisms that specify digit identities along the AP axis remain obscure. Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3 specify the digit identities of digits IV and III, respectively. Misexpression of Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV and digit II to digit III, respectively. Conversely, misexpression of their mutants VP16 Delta Tbx2 and VP16 Delta Tbx3 induced anterior transformation. In both cases, alterations in the expression of several markers (e.g., BMP2, Shh, and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated inhibition of interdigital BMP signaling, signaling which is pivotal in establishing digit identities. Hence, we conclude that Tbx3 specifies digit III, and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the interdigital BMP signaling cascade.
Suzuki
Takayuki
T
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0101, Japan.
Takeuchi
Jun
J
Koshiba-Takeuchi
Kazuko
K
Ogura
Toshihiko
T
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D053823:Hedgehog Proteins; D006614:Hindlimb / Q000002:abnormalities; D018398:Homeodomain Proteins / Q000235:genetics; D018878:Limb Buds / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D014034:Toes / Q000002:abnormalities*; D015534:Trans-Activators / Q000235:genetics*; D016212:Transforming Growth Factor beta
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta