Follistatin interacts with Noggin in the development of the axial skeleton

• Loss of Follistatin enhances Noggin mutant axial skeleton defects.
• In Noggin mutants, Follistatin aids in maintaining proper somite size.
• Follistatin affects somite size following somite formation.
• Follistatin limits BMP-mediated lateralization of paraxial mesoderm.
• Noggin and Gremlin1 mutation does not reduce somitic Follistatin activation.

When compared to single mutants for Follistatin or Noggin, we find that double mutants display a dramatic further reduction in trunk cartilage formation, particularly in the vertebral bodies and proximal ribs. Consistent with these observations, expression of the early sclerotome markers Pax1 and Uncx is diminished in Noggin;Follistatin compound mutants. In contrast, Sim1 expression expands medially in double mutants. As the onset of Follistatin expression coincides with sclerotome specification, we argue that the effect of Follistatin occurs after sclerotome induction. We hypothesize that Follistatin aids in maintaining proper somite size, and consequently sclerotome progenitor numbers, by preventing paraxial mesoderm from adopting an intermediate/lateral plate mesodermal fate in the Noggin-deficient state.