MIDKINE COUNTERACTS THE ACTIVIN SIGNAL IN MESODERM INDUCTION AND PROMOTES NEURAL FORMATION

Midkine (MK) is a heparin-binding growth factor that has been implicat ed in neural survival and differentiation, fibrinolysis, and carcinoge nesis. It is expressed in the nervous system during early Xenopus deve lopment. In the present study, we demonstrated that injection of veget al blastomeres with Xenopus MK at the 8-cell stage results in incomple te invagination. In the case of dorsal vegetal injection, hypertrophic neural tissue is produced. Animal caps isolated from embryos that hav e been injected with Xenopus MK and cultured with activin do not elong ate, and all mesoderm markers examined, including both head and trunk/ tail ones, are greatly diminished. In contrast, head-specific neural m arkers, XANF-1 and Xotx2, are induced, while trunk/tail neural markers , XIHbox6 and F-spondin, are decreased. Moreover, MK showes the same e ffects in animal caps injected with Xenopus Smad2 mRNA.