Dataset Information

?6 integrin subunit regulates cerebellar development.

ABSTRACT: Mutations in genes encoding several basal lamina components as well as their cellular receptors disrupt normal deposition and remodeling of the cortical basement membrane resulting in a disorganized cerebral and cerebellar cortex. The ?6 integrin was the first ? subunit associated with cortical lamination defects and formation of neural ectopias. In order to understand the precise role of ?6 integrin in the central nervous system (CNS), we have generated mutant mice carrying specific deletion of ?6 integrin in neuronal and glia precursors by crossing ?6 conditional knockout mice with Nestin-Cre line. Cerebral cortex development occurred properly in the resulting ?6 (fl/fl;nestin-Cre) mutant animals. Interestingly, however, cerebellum displayed foliation pattern defects although granule cell (GC) proliferation and migration were not affected. Intriguingly, analysis of Bergmann glial (BG) scaffold revealed abnormalities in fibers morphology associated with reduced processes outgrowth and altered actin cytoskeleton. Overall, these data show that ?6 integrin receptors are required in BG cells to provide a proper fissure formation during cerebellum morphogenesis.

SUBMITTER: Marchetti G

PROVIDER: S-EPMC3712000 | biostudies-literature | 2013 May-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

α6 integrin subunit regulates cerebellar development.

Marchetti Giovanni G De Arcangelis Adèle A Pfister Véronique V Georges-Labouesse Elisabeth E

Cell adhesion & migration 20130524 3

Mutations in genes encoding several basal lamina components as well as their cellular receptors disrupt normal deposition and remodeling of the cortical basement membrane resulting in a disorganized cerebral and cerebellar cortex. The α6 integrin was the first α subunit associated with cortical lamination defects and formation of neural ectopias. In order to understand the precise role of α6 integrin in the central nervous system (CNS), we have generated mutant mice carrying specific deletion of ...[more]

PMID: 23722246

Similar Datasets

Project description:Central nervous system leukemia (CNS-L) is caused by leukemic cells infiltrating into the meninges or brain parenchyma and remains the main reason for disease relapse. Currently, it is hard to detect CNS-L accurately by clinically available imaging models due to the relatively low amount of tumor cells, confined blood supply, and the inferior glucose metabolism intensity. Recently, integrin α6-laminin interactions have been identified to mediate CNS-L, which suggests that integrin α6 may be a promising molecular imaging target for the detection of CNS-L. The acute lymphoblastic leukemia (ALL) cell line NALM6 stabled and transfected with luciferase was used to establish the CNS-L mouse model. CNS-L-bearing mice were monitored and confirmed by bioluminescence imaging. Three of our previously developed integrin α6-targeted peptide-based molecular imaging agents, Cy5-S5 for near-infrared fluorescence (NIRF), Gd-S5 for magnetic resonance (MR), and 18F-S5 for positron emission tomography (PET) imaging, were employed for the molecular imaging of these CNS-L-bearing mice. Bioluminescence imaging showed a local intensive signal in the heads among CNS-L-bearing mice; meanwhile, Cy5-S5/NIRF imaging produced intensive fluorescence intensity in the same head regions. Moreover, Gd-S5/MR imaging generated superior MR signal enhancement at the site of meninges, which were located between the skull bone and brain parenchyma. Comparatively, MR imaging with the clinically available MR enhancer Gd-DTPA did not produce the distinguishable MR signal in the same head regions. Additionally, 18F-S5/PET imaging also generated focal radio-concentration at the same head regions, which generated nearly 5-times tumor-to-background ratio compared to the clinically available PET radiotracer 18F-FDG. Finally, pathological examination identified layer-displayed leukemic cells in the superficial part of the brain parenchyma tissue, and immunohistochemical staining confirmed the overexpression of the integrin α6 within the lesion. These findings suggest the potential application of these integrin α6-targeted molecular imaging agents for the accurate detection of CNS-L.

Dataset Information

?6 integrin subunit regulates cerebellar development.

Publications

α6 integrin subunit regulates cerebellar development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets