We thank Dr. Andy Dudley for his help in designing mouse genotyping strategies. We also thank Jose Rivera-Feliciano and Dr. Douglas Kim for helpful discussions. We are immensely grateful to Drs. Brigid Hogan and Holger Kulessa for their kind gift of the Bmp4 conditional allele and Drs. Liz Robertson and Andy Dudley for the Bmp7 knockout allele. We would like to acknowledge the help of Dr. Ernestina Schipani and Jan Saxton for help with histology. This manuscript is dedicated to the memory of Dr. Holger Kulessa, whose efforts contributed to the groundwork for this study and whose dedication and intense commitment to excellence in science are greatly missed. Competing interests. The authors have declared that no competing interests exist. A previous version of this article appeared as an Early Online Release on November 6, 2006 (doi:10.1371/journal.pgen.0020216.eor). Author contributions. AB, KT, BDH, VR, and CJT conceived and designed the experiments. AB, KT, KC, and BDH performed the experiments. AB, KT, VR, and CJT analyzed the data. AB and KT wrote the paper. Funding. This work was supported by a grant from the National Institutes of Health (P01 DK56246 to CJT) and by funds from the Forsyth Institute and Harvard School of Dental Medicine (to VR). Abbreviations AER apical ectodermal ridge BMP bone morphogenetic protein E embryonic day FGF fibroblast growth factor SHH Sonic Hedgehog Shh sonic hedgehog ZPA zone of polarizing activity