title: FGF signaling enhances a sonic hedgehog negative feedback loop at the initiation of spinal cord ventral patterning.
abstract: A prevalent developmental mechanism for the assignment of cell identities is the production of spatiotemporal concentration gradients of extracellular signaling molecules that are interpreted by the responding cells. One of such signaling systems is the Shh gradient that controls neuronal subtype identity in the ventral spinal cord. Using loss and gain of function approaches in chick and mouse embryos, we show here that the fibroblast growth factor (FGF) signaling pathway is required to restrict the domains of ventral gene expression as neuroepithelial cells become exposed to Shh during caudal extension of the embryo. FGF signaling activates the expression of the Shh receptor and negative pathway regulator Patched 2 (Ptch2) and therefore can enhance a negative feedback loop that restrains the activity of the pathway. Thus, we identify one of the mechanisms by which FGF signaling acts as a modulator of the onset of Shh signaling activity in the context of coordination of ventral patterning and caudal axis extension. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 956-971, 2016.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.
authors.forename: Aixa V
authors.initials: AV
authors.lastname: Morales
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Espeso-Gil
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.|CIBER de Enfermedades Raras, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ocaña
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.|CIBER de Enfermedades Raras, Spain.|Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-UAM, Cantoblanco, 28049, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Nieto-Lopez
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Calleja
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.|CIBER de Enfermedades Raras, Spain.|Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-UAM, Cantoblanco, 28049, Spain.
authors.forename: Paola
authors.initials: P
authors.lastname: Bovolenta
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, 21702, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lewandoski
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, 28002, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Diez Del Corral
mesh_terms: D000818:Animals; D002642:Chick Embryo; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D066151:Spinal Cord Ventral Horn / Q000196:embryology / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D005346:Fibroblast Growth Factors
keywords: FGF; Ptch; Shh; chick embryo; gene regulatory network; mouse embryo; neural tube