Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification

摘要: Rostro-caudal patterning of vertebrates depends on the temporally progressive activation HOX genes within axial stem cells that fuel embryo elongation. Whether pace sequential genes, 'HOX clock', is controlled by intrinsic chromatin-based timing mechanisms or temporal changes in extrinsic cues remains unclear. Here, we studied clock pacing human pluripotent cell-derived progenitors differentiating into diverse spinal cord motor neuron subtypes. We show caudal a dynamic increase FGF signaling. Blocking pathway stalled induction while precocious FGF, alone with GDF11 ligand, accelerated clock. Cells differentiated under generated appropriate posterior subtypes found along embryonic cord. The thus dynamically regulated exposure to secreted cues. Its manipulation factors provides synchronized access multiple neuronal distinct rostro-caudal identities for basic and translational applications.This article has an associated 'The people behind papers' interview.