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The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10

Jennifer K. Ng^1,*, Yasuhiko Kawakami^1,*, Dirk Büscher^1,*, Ángel Raya^1,*, Tohru Itoh¹, Christopher M. Koth¹, Concepción Rodríguez Esteban¹, Joaquín Rodríguez-León², Deborah M. Garrity³, Mark C. Fishman³ and Juan Carlos Izpisúa Belmonte^1,

¹ The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099. USA
² Instituto Gulbenkian de Ciencia, Rua Da Quinta Grande n 6, 2780-901 Oeiras, Portugal
³ Cardiovascular Research Center, Massachusetts General Hospital, 149 13^th Street, Charlestown, MA 02129, USA

Author for correspondence (e-mail: belmonte{at}salk.edu)

Accepted 21 August 2002

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.

Key words: T-box, Tbx5, Wnt2b, Fgf10, Pectoral fin, Limb, Zebrafish, Chick, heartstrings

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