BMP signaling and HOX transcription factors in limb development

Limb development, a complicated biological event that includes diverse processes such as three-dimensional patterning, cartilage and bone differentiation and programmed cell death, or apoptosis, is regulated by a network of signal molecules that work in concert to ensure proper morphogenesis. Bone Morphogenetic Proteins (BMPs), members of the TGF superfamily, play a pivotal role in the signaling network and are involved in nearly all processes associated with limb development. While the canonical BMP/Smad signaling cascade has been clarified, the pathway by itself does not explain how BMPs exert such diverse functions. The answer may lie in the crosstalk between BMPs and other signaling pathways, as well as the diverse transcription factors used by BMPs. The major objective of this review is to summarize the main functions of BMP signaling during limb development and to describe the crosstalk between BMPs and other signaling molecules such as Wnts, FGFs and Shh. In addition, distinct transcription factors downstream of BMP signaling will be discussed. Among the various transcription factors, we will focus on the Hox family of proteins, which play an important role in limb patterning.