Interactions between FGFs and BMPs in the control of programmed cell death in the developing limb

Abstract

Programmed cell death (PCD) has a major role in vertebrate limb morphogenesis. In the developing chick embryo four areas of PCD, the anterior necrotic zone (ANZ), the posterior necrotic zone (PNZ), the opaque patch (OP) and the interdigital necrotic zones (INZ) are responsible for sculpturing the shape of the limb. There is abundant evidence showing that BMPs are responsible for triggering apoptosis in the limb mesoderm (Macias et al., 1997). However, BMPs are at the same time the signals acounting for chondrogenesis (Zou et al., 1997; Pizette and Niswander, 2000). Local application of BMPs into the undifferentiated limb mesoderm causes apoptosis (Fig. 1A). However, the same treatment applied into the prechondrogenic mesenchyme results in massive chondrogenesis (Fig. 1 B,C). Thus, the stage of differentiation of the mesodermal target tissue appears to have a major influence between the two opposite effects of BMPs. FGFs are the signals responsible for maintaining the limb mesoderm in an undifferentiated and proliferating state (Martin,