Glycogen synthase kinase 3 promotes multicellular development over unicellular encystation in encysting Dictyostelia.

Background: Glycogen synthase kinase 3 (GSK3) regulates many cell fate decisions in animal development. In multicellular structures of the group 4 dictyostelid Dictyostelium discoideum , GSK3 promotes spore over stalk-like differentiation. We investigated whether, similar to other sporulation-inducing genes such as cAMP-dependent protein kinase (PKA), this role of GSK3 is derived from an ancestral role in encystation of unicellular amoebas.

Results: We deleted GSK3 in Polysphondylium pallidum , a group 2 dictyostelid which has retained encystation as an alternative survival strategy. Loss of GSK3 inhibited cytokinesis of cells in suspension, as also occurs in D. discoideum , but did not affect spore or stalk differentiation in P. pallidum . However, gsk3 - amoebas entered into encystation under conditions that in wild type favour aggregation and fruiting body formation. The gsk3 - cells were hypersensitive to osmolytes, which are known to promote encystation, and to cyst-inducing factors that are secreted during starvation. GSK3 was not itself regulated by these factors, but inhibited their effects.

Conclusions: Our data show that GSK3 has a deeply conserved role in controlling cytokinesis, but not spore differentiation in Dictyostelia. Instead, in P. pallidum , one of many Dictyostelia that like their solitary ancestors can still encyst to survive starvation, GSK3 promotes multicellular development into fruiting bodies over unicellular encystment.