RGM Regulates BMP-Mediated Secondary Axis Formation in the Sea Anemone Nematostella vectensis

•RGM regulates BMP-dependent secondary axis formation and patterning in Nematostella•A pSmad1/5/8 gradient is activated on the side opposite BMP/RGM expression•RGM has distinct functions in symmetry break and shaping the pSmad1/5/8 gradient•Asymmetry of BMP or RGM expression is sufficient to direct the pSmad1/5/8 gradient

SummaryPatterning of the metazoan dorsoventral axis is mediated by a complex interplay of BMP signaling regulators. Repulsive guidance molecule (RGM) is a conserved BMP coreceptor that has not been implicated in axis specification. We show that NvRGM is a key positive regulator of BMP signaling during secondary axis establishment in the cnidarian Nematostella vectensis. NvRGM regulates first the generation and later the shape of a BMP-dependent Smad1/5/8 gradient with peak activity on the side opposite the NvBMP/NvRGM/NvChordin expression domain. Full knockdown of Smad1/5/8 signaling blocks the formation of endodermal structures, the mesenteries, and the establishment of bilateral symmetry, while altering the gradient through partial NvRGM or NvBMP knockdown shifts the boundaries of asymmetric gene expression and the positioning of the mesenteries along the secondary axis. These findings provide insight into the diversification of axis specification mechanisms and identify a previously unrecognized role for RGM in BMP-mediated axial patterning.

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