The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10.
A major gap in our knowledge of development is how the growth and identity of tissues and organs are linked during embryogenesis. The vertebrate limb is one of the best models to study these processes. Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity, is both necessary and sufficient for limb outgrowth. We find that Tbx5 functions downstream of WNT signaling to regulate Fgf10, which, in turn, maintains Tbx5 expression during limb outgrowth. Furthermore, our results indicate that Tbx5 and Wnt2b function together to initiate and specify forelimb outgrowth and identity. The molecular interactions governed by members of the T-box, Wnt and Fgf gene families uncovered in this study provide a framework for understanding not only limb development, but how outgrowth and identity of other tissues and organs of the embryo may be regulated.
Ng
Jennifer K
JK
The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099. USA.
Kawakami
Yasuhiko
Y
Büscher
Dirk
D
Raya
Angel
A
Itoh
Tohru
T
Koth
Christopher M
CM
Rodríguez Esteban
Concepción
C
Rodríguez-León
Joaquín
J
Garrity
Deborah M
DM
Fishman
Mark C
MC
Izpisúa Belmonte
Juan Carlos
JC
D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D004625:Embryo, Nonmammalian; D005121:Extremities / Q000196:embryology*; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D018878:Limb Buds / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D051526:Fibroblast Growth Factor 10; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C520413:fgf10a protein, zebrafish; C492033:wnt2ba protein, zebrafish; D005346:Fibroblast Growth Factors