title: Laminin α1 is essential for mouse cerebellar development.
abstract: Laminin α1 (Lama1), which is a subunit of laminin-1 (laminin-111), a heterotrimeric ECM protein, is essential for embryonic development and promotes neurite outgrowth in culture. Because the deletion of Lama1 causes lethality at early embryonic stages in mice, the in vivo role of Lama1 in neural development and functions has not yet been possible to determine. In this study, we generated conditional Lama1 knockout (Lama1(CKO)) mice in the epiblast lineage using Sox2-Cre mice. These Lama1(CKO) mice survived, but displayed behavioral disorders and impaired formation of the cerebellum. Deficiency of Lama1 in the pial basement membrane of the meninges resulted in defects in the conformation of the meninges. During cerebellar development, Lama1 deficiency also caused a decrease in the proliferation and migration of granule cell precursors, disorganization of Bergmann glial fibers and endfeet, and a transient reduction in the activity of Akt. A marked reduction in numbers of dendritic processes in Purkinje cells was observed in Lama1(CKO) mice. Together, these results indicate that Lama1 is required for cerebellar development and functions.
authors: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Naoki
authors: N
authors: Ichikawa-Tomikawa
authors: Junko
authors: J
authors: Ogawa
authors: Vanessa
authors: V
authors: Douet
authors: Zhuo
authors: Z
authors: Xu
authors: Yuji
authors: Y
authors: Kamikubo
authors: Takashi
authors: T
authors: Sakurai
authors: Shinichi
authors: S
authors: Kohsaka
authors: Hideki
authors: H
authors: Chiba
authors: Nobutaka
authors: N
authors: Hattori
authors: Yoshihiko
authors: Y
authors: Yamada
authors: Eri
authors: E
authors: Arikawa-Hirasawa
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development*; D017630:Connexins / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008578:Meninges / Q000002:abnormalities* / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D016501:Neurites / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D017630:Connexins; D007797:Laminin; C084098:laminin A; D051058:Oncogene Protein v-akt