RGD Reference Report - Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. - Rat Genome Database

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Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice.

Authors: Klezovitch, O  Fernandez, TE  Tapscott, SJ  Vasioukhin, V 
Citation: Klezovitch O, etal., Genes Dev 2004 Mar 1;18(5):559-71.
RGD ID: 1300301
Pubmed: PMID:15037549   (View Abstract at PubMed)
PMCID: PMC374237   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.1178004   (Journal Full-text)

Disruption of cell polarity is seen in many cancers; however, it is generally considered a late event in tumor progression. Lethal giant larvae (Lgl) has been implicated in maintenance of cell polarity in Drosophila and cultured mammalian cells. We now show that loss of Lgl1 in mice results in formation of neuroepithelial rosette-like structures, similar to the neuroblastic rosettes in human primitive neuroectodermal tumors. The newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally. A large proportion of Lgl1(-/-) neural progenitor cells fail to exit the cell cycle and differentiate, and, instead, continue to proliferate and die by apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack of differentiation. These results reveal a critical role for mammalian Lgl1 in regulating of proliferation, differentiation, and tissue organization and demonstrate a potential causative role of disruption of cell polarity in neoplastic transformation of neuroepithelial cells.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hydrocephalus  ISOLlgl1 (Mus musculus)1300301; 1300301 RGD 
hydrocephalus  IMP 1300301 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Llgl1  (LLGL scribble cell polarity complex component 1)

Genes (Mus musculus)
Llgl1  (LLGL1 scribble cell polarity complex component)

Genes (Homo sapiens)
LLGL1  (LLGL scribble cell polarity complex component 1)

Objects referenced in this article
Gene DLG4 discs large MAGUK scaffold protein 4 Homo sapiens
Gene Dlg4 discs large MAGUK scaffold protein 4 Mus musculus
Gene H3f3a H3.3 histone A Mus musculus
Gene Llgl2 LLGL2 scribble cell polarity complex component Mus musculus
Gene Meox2 mesenchyme homeobox 2 Mus musculus
Gene Myl12b myosin, light chain 12B, regulatory Mus musculus
Gene Numb NUMB endocytic adaptor protein Mus musculus
Gene Shroom3 shroom family member 3 Mus musculus
Gene Dlg4 discs large MAGUK scaffold protein 4 Rattus norvegicus

Additional Information