title: Developmental disruptions underlying brain abnormalities in ciliopathies.
abstract: Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies.
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jiami
authors.initials: J
authors.lastname: Guo
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Holden
authors.initials: H
authors.lastname: Higginbotham
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Li
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Nichols
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Josua
authors.initials: J
authors.lastname: Hirt
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ghukasyan
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Anton
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000235:genetics*; D002540:Cerebral Cortex / Q000196:embryology*; D002923:Cilia / Q000235:genetics*; D005260:Female; D015723:Gene Library; D006801:Humans; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D011247:Pregnancy; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering