Molecular Control of Interdigital Cell Death and Cell Differentiation by Retinoic Acid during Digit Development

The precise coordination of cell death and cell differentiation during the formation of developing digits is essential for generating properly shaped limbs. Retinoic acid (RA) has a fundamental role in digit development; it promotes or inhibits the molecular expression of several critical genes. This control of gene expression establishes molecular cascades that enable both the commencement of cell death and the inhibition of cell differentiation. In this review, we focus on the antagonistic functions between RA and fibroblast growth factor (FGF) signaling in the control of cell death and between RA and transforming growth factor beta (TGFβ) signaling in the control of cell differentiation.