BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration.

Planarians can be cut into irregularly shaped fragments capable of regenerating new and complete organisms. Such regenerative capacities involve a robust ability to restore bilateral symmetry. We have identified three genes needed for bilaterally asymmetric fragments to regenerate missing body parts. These genes are candidate components of a signaling pathway that controls the dorsal-ventral patterning of many animal embryos: a BMP1/Tolloid-like gene (smedolloid-1), a SMAD4-like gene (smedsmad4-1), and a BMP2/4/DPP-like gene (smedbmp4-1). BMP signaling was involved in the formation of new tissues at the midline of regeneration, the dorsal-ventral patterning of new tissues, and the maintenance of the dorsal-ventral pattern of existing adult tissue in homeostasis. smedbmp4-1 was normally expressed at the dorsal midline. Asymmetric fragments lacking a midline displayed new smedbmp4-1 expression prior to formation of a regenerative outgrowth (blastema). Asymmetric fragments containing the midline displayed expanded smedbmp4-1 expression towards the wound. We suggest injured animals that lack left-right symmetry reset their midline through modulation of BMP activity as an early and necessary event in regeneration.