Ednrb2 orients cell migration towards the dorsolateral neural crest pathway and promotes melanocyte differentiation.

Endothelin receptors B (Ednrb) are involved in the development of the enteric and melanocytic lineages, which originate from neural crest cells (NCCs). In mice, trunk NCCs and their derivatives express only one Ednrb. In quail, trunk NCCs express two Ednrb: Ednrb and Ednrb2. Quail Ednrb is expressed in NCCs migrating along the ventral pathway, which gives rise to the peripheral nervous system, including enteric ganglia. Ednrb2 is upregulated in NCCs before these cells enter the dorsolateral pathway. The NCCs migrating along the dorsolateral pathway are melanocyte precursors. We analyzed the in vitro differentiation and in ovo migration of mouse embryonic stem (ES) cells expressing and not expressing Ednrb2. We generated a series of transfected ES cell lines expressing Ednrb2. This receptor, like Ednrb, oriented genuine ES cells towards melanocyte lineage differentiation in vitro. The in ovo migration of Ednrb2-expressing ES cells was massively oriented towards the dorsolateral pathway, unlike that of WT or Ednrb-expressing ES cells. Thus, Ednrb2 is involved in melanoblast differentiation and migration.