Fig 9. S1pr2 signalling regulates pancreatic lineage allocation and specification.

S1pr2 signalling attenuates Notch signalling to promote the segregation of tip MPCs that will give rise to acinar progenitors and bipotent trunk progenitors and, in the latter, to promote the generation of endocrine progenitors via Ngn3 stabilisation. These are two temporally distinct steps shown here as one for simplicity. Ngn3 is stabilised post-translationally in Notch^low cells [19]. Additionally, S1p signalling stabilises YAP to enable progenitor survival. G_αi activation mediates the stabilisation of the YAP protein to enable endocrine specification. Both YAP stabilisation and Notch down-regulation are necessary for endocrine specification.