title: Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis.
abstract: Midbrain dopaminergic (mDA) neurons are generated in the ventral midbrain floor plate depending on Sonic Hedgehog (SHH) signaling for induction. Primary cilia transduce canonical SHH signals. Loss of intraflagellar transport protein IFT88, essential for ciliary function, disrupts SHH signaling in the ventral midbrain and results in the reduction in mDA progenitors and neurons. We investigate whether conditional inactivation of the kinesin motor protein KIF3A recapitulates phenotypes observed in conditionalIft88mutants. ConditionalKif3ainactivation reduced the mDA progenitor domain size, but did not result in mDA neuron reduction,most likely because of a delayed loss of cilia and delayed inactivation of SHH signaling. We thereby define a precise spatiotemporal window within which primary cilia-dependent SHH signaling determines mDA fate.
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn , Bonn, Germany.
authors.forename: Mary
authors.initials: M
authors.lastname: Gazea
authors.affiliation: Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany; Institute of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Tasouri
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn , Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heigl
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn , Bonn, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Bosch
authors.affiliation: Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany; Institute of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany; University of New England, College of Osteopathic Medicine, Department of Biomedical Sciences, Center for Excellence in the Neurosciences, Biddeford, ME, USA.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Tucker
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn , Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blaess
keywords: IFT88; KIF3A; Sonic hedgehog; WNT; dopaminergic neurons; intraflagellar transport; midbrain; primary cilia