One of the most perplexing quandries of FOP is the
great toe malformation. "Okay," one might say, "too much BMP
activity causes too much bone. That is easy to understand; but
what's going on with the big toe?"
While we do not yet know all of the answers, we do
know this:
Mutant ACVR1 is involved in the malformation of the
great toe. When normal copies of the ACVR1 gene are injected
into the developing limb buds of chicken embryos, not much
happens, but when mutant (FOP) copies of the ACVR1 gene are
injected into the developing limb buds, the chickens are born with
malformation of the great toes. These extraordinary findings from
the laboratory of our collaborators Drs. Petra Seemann and Stefan
Mundlos at the Max Planck Institute of Molecular Genetics in
Berlin, Germany are beginning to dramatically enhance our
understanding of the actions of the overactive FOP gene and
receptor during development.
