title: FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk.
abstract: Coordination between functionally related adjacent tissues is essential during development. For example, formation of trunk neural crest cells (NCCs) is highly influenced by the adjacent mesoderm, but the molecular mechanism involved is not well understood. As part of this mechanism, fibroblast growth factor (FGF) and retinoic acid (RA) mesodermal gradients control the onset of neurogenesis in the extending neural tube. In this paper, using gain- and loss-of-function experiments, we show that caudal FGF signaling prevents premature specification of NCCs and, consequently, premature epithelial-mesenchymal transition (EMT) to allow cell emigration. In contrast, rostrally generated RA promotes EMT of NCCs at somitic levels. Furthermore, we show that FGF and RA signaling control EMT in part through the modulation of elements of the bone morphogenetic protein and Wnt signaling pathways. These data establish a clear role for opposition of FGF and RA signaling in control of the timing of NCC EMT and emigration and, consequently, coordination of the development of the central and peripheral nervous system during vertebrate trunk elongation.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain. aixamorales@cajal.csic.es
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Martínez-Morales
authors.forename: Ruth
authors.initials: R
authors.lastname: Diez del Corral
authors.forename: Isabel
authors.initials: I
authors.lastname: Olivera-Martínez
authors.forename: Alejandra C
authors.initials: AC
authors.lastname: Quiroga
authors.forename: Raman M
authors.initials: RM
authors.lastname: Das
authors.forename: Julio A
authors.initials: JA
authors.lastname: Barbas
authors.forename: Kate G
authors.initials: KG
authors.lastname: Storey
authors.forename: Aixa V
authors.initials: AV
authors.lastname: Morales
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle; D002465:Cell Movement; D002490:Central Nervous System / Q000196:embryology; D002642:Chick Embryo; D018274:Electroporation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D017933:Peripheral Nervous System / Q000196:embryology; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis; D014212:Tretinoin / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases