Influence of FGF4 on digit morphogenesis during limb development in the mouse

Much of what we currently know about digit morphogenesis during limb develo pment is deduced from embryonic studies in the chick. In this study, we use d ex utero surgical procedures to study digit morphogenesis during mouse em bryogenesis. Our studies reveal some similarities; however, we have found c onsiderable differences in how the chick and the mouse autopods respond to experimentation. first, we are not able to induce ectopic digit formation f rom interdigital cells as a result of wounding or TGF beta-1 application in the mouse, in contrast to what is observed in the chick. Second, FGF4, whi ch inhibits the formation of ectopic digits in the chick, induces a digit b ifurcation response in the mouse. We demonstrate with cell marking studies that this bifurcation response results from a reorganization of the prechon drogenic tip of the digit rudiment. The FGF4 effect on digit morphogenesis correlates with changes in the expression of a number of genes, including M sx1, Igf2, and the posterior members of the HoxD cluster. In addition, the bifurcation response is digit-specific, being restricted to digit IV. We pr opose that FGF4 is an endogenous signal essential for skeletal branching mo rphogenesis in the mouse. This work stresses the existence of major differe nces between the chick and the mouse in how digit morphogenesis is regulate d and is thus consistent with the view that vertebrate digit evolution is a relatively recent event. Finally, we discuss the relationship between the digit IV bifurcation restriction and the placement of the metapterygial axi s in the evolution of the tetrapod limb. (C) 2000 Academic Press.