WNT Signals Control FGF-Dependent Limb Initiation and AER Induction in the Chick Embryo

• Published in: Cell 2001-03, Vol.104 (6), p.891-900
• Main Authors: Kawakami, Yasuhiko, Capdevila, Javier, Büscher, Dirk, Itoh, Tohru, Esteban, Concepción Rodrı́guez, Belmonte, Juan Carlos Izpisúa
• Format: Article
• Language: English
• Subjects: Animals; Avian Proteins; b-catenin; beta Catenin; Chick Embryo - physiology; Cytoskeletal Proteins - physiology; Ectoderm - physiology; Fgf-10 gene; Fgf-8 gene; Fibroblast Growth Factor 10; Fibroblast Growth Factor 8; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - physiology; Gene Expression Regulation, Developmental; Limb Buds - physiology; Mesoderm - physiology; Mitogens - physiology; Morphogenesis; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Signal Transduction; Trans-Activators; Wings, Animal - embryology; Wnt Proteins; Wnt-2b gene; Wnt-3a gene; Wnt-8c gene; Wnt2 Protein; Zebrafish Proteins
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(01)00285-9

A regulatory loop between the fibroblast growth factors FGF-8 and FGF-10 plays a key role in limb initiation and AER induction in vertebrate embryos. Here, we show that three WNT factors signaling through β-catenin act as key regulators of the FGF-8/FGF-10 loop. The Wnt-2b gene is expressed in the intermediate mesoderm and the lateral plate mesoderm in the presumptive chick forelimb region. Cells expressing Wnt-2b are able to induce Fgf-10 and generate an extra limb when implanted into the flank. In the presumptive hindlimb region, another Wnt gene, Wnt-8c, controls Fgf-10 expression, and is also capable of inducing ectopic limb formation in the flank. Finally, we also show that the induction of Fgf-8 in the limb ectoderm by FGF-10 is mediated by the induction of Wnt-3a. Thus, three WNT signals mediated by β-catenin control both limb initiation and AER induction in the vertebrate embryo.