title: LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-type lamins.
abstract: Nuclear lamins are major components of the nuclear lamina, and play essential roles in supporting the nucleus and organizing nuclear structures. While a large number of clinically important mutations have been mapped to the LMNA gene in humans, very few mutations have been associated with the B-type lamins. We have shown that lamin B2-deficiency in mice results in severe brain abnormalities. While the early stages of forebrain development in lamin B2-deficient mice appear to be normal, cortical neurons fail to migrate and organize into proper layers within the cerebral cortex. The morphogenesis of the hippocampus and cerebellum is also severely impaired. These phenotypes are reminiscent of lissencephaly, a human brain developmental disorder characterized by an abnormal neuronal migration. Most mutations in lissencephaly patients affect cytoplasmic regulators of nuclear translocation, which is a crucial step in neuronal migration. The phenotypes of lamin B2-deficient mice suggest that lamin B2 may also play a key role in nuclear translocation. Potential mechanisms for lamin B2 involvement, which include mechanical and non-mechanical roles, and participation in LINC complexes in the nuclear envelope, are discussed along with evidence that lamins B1 and B2 play distinct, cell-specific functions.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. coffinie@ucla.edu
authors.forename: Catherine
authors.initials: C
authors.lastname: Coffinier
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D034921:Lamin Type B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism
chemical_list: D034921:Lamin Type B