Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons

Neuronal migration is essential for the development of the mammalian brain. Here, we document severe defects in neuronal migration and reduced numbers of neurons in lamin B1-deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear shape of cortical neurons; many neurons...

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Bibliographic Details
Published in:Molecular biology of the cell 2011-12, Vol.22 (23), p.4683-4693
Main Authors: Coffinier, Catherine, Jung, Hea-Jin, Nobumori, Chika, Chang, Sandy, Tu, Yiping, Barnes, 2nd, Richard H, Yoshinaga, Yuko, de Jong, Pieter J, Vergnes, Laurent, Reue, Karen, Fong, Loren G, Young, Stephen G
Format: Article
Language:English
Subjects:
Animals
Atrophy
Brain
Brain - abnormalities
Brain - embryology
Brain - growth & development
Cell migration
Cortex
Elongation
Forebrain
Lamin Type B - genetics
Lamin Type B - metabolism
Lamins
Mice
Mice, Knockout
Neurons
Neurons - metabolism
Neurons - pathology
Nuclear Lamina
Prosencephalon - abnormalities
Prosencephalon - growth & development
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Summary:Neuronal migration is essential for the development of the mammalian brain. Here, we document severe defects in neuronal migration and reduced numbers of neurons in lamin B1-deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear shape of cortical neurons; many neurons contained a solitary nuclear bleb and exhibited an asymmetric distribution of lamin B2. In contrast, lamin B2 deficiency led to increased numbers of neurons with elongated nuclei. We used conditional alleles for Lmnb1 and Lmnb2 to create forebrain-specific knockout mice. The forebrain-specific Lmnb1- and Lmnb2-knockout models had a small forebrain with disorganized layering of neurons and nuclear shape abnormalities, similar to abnormalities identified in the conventional knockout mice. A more severe phenotype, complete atrophy of the cortex, was observed in forebrain-specific Lmnb1/Lmnb2 double-knockout mice. This study demonstrates that both lamin B1 and lamin B2 are essential for brain development, with lamin B1 being required for the integrity of the nuclear lamina, and lamin B2 being important for resistance to nuclear elongation in neurons.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e11-06-0504