FGF Modulates the Axial Identity of Trunk hPSC-Derived Neural Crest but Not the Cranial-Trunk Decision

Summary: The neural crest is a transient embryonic tissue that gives rise to a multitude of derivatives in an axially restricted manner. An in vitro counterpart to neural crest can be derived from human pluripotent stem cells (hPSCs) and can be used to study neural crest ontogeny and neurocristopathies, and to generate cells for therapeutic purposes. In order to successfully do this, it is critical to define the specific conditions required to generate neural crest of different axial identities, as regional restriction in differentiation potential is partly cell intrinsic. WNT and FGF signaling have been implicated as inducers of posterior fate, but the exact role that these signals play in trunk neural crest formation remains unclear. Here, we present a fully defined, xeno-free system for generating trunk neural crest from hPSCs and show that FGF signaling directs cells toward different axial identities within the trunk compartment while WNT signaling is the primary determinant of trunk versus cranial identity. : In this article, Hackland and colleagues present a highly efficient system for deriving trunk neural crest from hPSCs. They show using this system that FGF signaling dictates the axial identity of cells within the trunk compartment, but that the cranial versus trunk decision is FGF independent and is instead determined by the magnitude of WNT signaling. Keywords: trunk neural crest, WNT, FGF, human pluripotent stemm cells, CDX2, OTX2, Brachyury, SOX2, axial progenitors, NMPs