Antagonistic effects of FGF4 on BMP induction of apoptosis and chondrogenesis in the chick limb bud

Abstract

In an effort to define the roles of bone morphogenic proteins (BMPs) and fibroblast growth factors (FGFs) during chick limb development more closely, we have implanted beads impregnated with these growth factors into chick limb buds between stages 20 and 26. Embryos were sacrificed at the time the bone chondrocyte condensations first appear (stages 27-28). Implantation of beads containing BMPs at the earlier stages (20-22) caused apoptosis to occur, in the most severe cases leading to complete limb degeneration. Application of FGF4, either in the same, or in a different bead, prevented the BMP-induced apoptosis. We argue that the apoptosis observed on removal of the AER prior to stage 23 of development could be brought about by BMPs. The action of epithelial FGF in preventing BMP-mediated apoptosis in the mesenchyme would define a novel aspect of epithelial-mesenchymal interactions. Implanting the BMP4 beads into the core of the limb bud a day later (stages 25-26) caused intense chondrogenesis rather than apoptosis. FGF4 could again nullify this effect and by itself caused a reduction in bone size. This is the reverse of the functional relationship these growth factors have in mouse tooth specification (where it is BMP4 that inhibits the FGF8 function), and suggests that the balance between the effects of FGFs and BMPs could control the size of the chondrocyte precursor cell pool. In this way members of these two growth factor families could control the size of appendages when they are initially formed.

Regulation and role of Sox9 in cartilage formation

“…6A) indicating that BMP can mediate the induction of Sox9. Grafting BMP beads earlier than stage 25 did not result in ectopic chondrogenesis or induction of Sox9 (Buckland et al, 1998 and data not shown) indicating that chondrogenic competency in response to BMP signalling changes during limb development.…”

“…Implantation of BMP beads into stage 25 and older chick limbs results in ectopic chondrogenesis (Buckland et al, 1998). To test whether this effect correlated with induction of Sox9 we grafted beads soaked in BMP2 into stage 25 chick limbs and assayed Sox9 expression 24 hours later.…”

Apoptosis in developmental and repair-related human tooth remodeling: A view from the inside

“…5). This effect may be time-dependent [42], since BMPs at a second time play a role in dental hard tissue formation [19,20]. In addition, it has been shown that apoptosis is accompanied by upregulation in the expression of transforming growth factor beta (TGFβ) [27], which is also essential for reparative dentinogenesis [19].…”

Interdigital webbing retention in bat wings illustrates genetic changes underlying amniote limb diversification

“…Intriguingly, Msx gene expression in bat wings suggests that Gremlin is not able to inhibit all Bmp signaling in the forelimb interdigits or that another factor activates Msx expression there. Fgfs have been proposed to be survival signals for a variety of tissues (15), and Fgf application has been shown to transiently block cell death in chick limb interdigits (16)(17)(18)(19). In mice, expression of a gain-of-function allele of Fgf4 results in persistent webbing between the digits (20) (24) but is strikingly different from other amniotes.…”