title: FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues.
abstract: Sonic hedgehog (SHH) is a secreted morphogen that regulates the patterning and growth of many tissues in the developing mouse embryo, including the central nervous system (CNS). We show that a member of the FK506-binding protein family, FKBP8, is an essential antagonist of SHH signaling in CNS development. Loss of FKBP8 causes ectopic and ligand-independent activation of the Shh pathway, leading to expansion of ventral cell fates in the posterior neural tube and suppression of eye development. Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development.
authors.affiliation: The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Bulgakov
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Eggenschwiler
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Hong
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
authors.forename: Tiansen
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D019521:Body Patterning; D002490:Central Nervous System / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology*; D005123:Eye / Q000033:anatomy & histology / Q000196:embryology; D018390:Gene Targeting; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C119437:Fkbp8 protein, mouse; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D022021:Tacrolimus Binding Proteins