title: Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse.
abstract: RIC8A is a noncanonical guanine nucleotide exchange factor for a subset of Gα subunits. RIC8A has been reported in different model organisms to participate in the control of mitotic cell division, cell signalling, development and cell migration. Still, the function of RIC8A in the mammalian nervous system has not been sufficiently analysed yet. Adult mice express RIC8A in the brain regions involved in the regulation of memory and emotional behaviour. To elucidate the role of RIC8A in mammalian neurogenesis we have inactivated Ric8a in neural precursor cells using Cre/Lox system. As a result, the conditional knockout mice were born at expected Mendelian ratio, but died or were cannibalized by their mother within 12 h after birth. The cerebral cortex of the newborn Nes;Ric8a(CKO) mice was thinner compared to littermates and the basement membrane was discontinuous, enabling migrating neurons to invade to the marginal zone. In addition, the balance between the planar and oblique cell divisions was altered, influencing the neuron production. Taken together, RIC8A has an essential role in the development of mammalian nervous system by maintaining the integrity of pial basement membrane and modulating cell division.
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Keiu
authors: K
authors: Kask
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Katrin
authors: K
authors: Ruisu
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Laura
authors: L
authors: Tikker
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Kirstin
authors: K
authors: Karis
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Merly
authors: M
authors: Saare
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Riho
authors: R
authors: Meier
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Alar
authors: A
authors: Karis
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Tambet
authors: T
authors: Tõnissoo
authors: Department of Developmental Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia St., Tartu 51010, Estonia.
authors: Margus
authors: M
authors: Pooga
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D003643:Death; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009468:Neuromuscular Diseases / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C485884:Ric8a protein, mouse
keywords: RIC8A; basement membrane; cell division; cerebral cortex; neurogenesis