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

Author:

Coffinier Catherine1,Jung Hea-Jin2,Nobumori Chika1,Chang Sandy1,Tu Yiping1,Barnes Richard H.1,Yoshinaga Yuko3,de Jong Pieter J.3,Vergnes Laurent4,Reue Karen4,Fong Loren G.1,Young Stephen G.14

Affiliation:

1. Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095

2. Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095

3. Children's Hospital Oakland Research Institute, Oakland, CA 94609

4. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095

Abstract

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.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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