The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse

PLoS Genet. 2013;9(1):e1003261. doi: 10.1371/journal.pgen.1003261. Epub 2013 Jan 31.

Abstract

The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this topic has provided novel important clues about nuclear lamina function. These studies have contributed to the knowledge that the lamina constitutes a complex multifunctional platform combining both structural and regulatory functions. Here, we report that, in addition to the previously demonstrated significance for somatic cell differentiation and maintenance, the nuclear lamina is also an essential determinant for germ cell development. Both male and female mice lacking the short meiosis-specific A-type lamin C2 have a severely defective meiosis, which at least in the male results in infertility. Detailed analysis revealed that lamin C2 is required for telomere-driven dynamic repositioning of meiotic chromosomes. Loss of lamin C2 affects precise synapsis of the homologs and interferes with meiotic double-strand break repair. Taken together, our data explain how the nuclear lamina contributes to meiotic chromosome behaviour and accurate genome haploidization on a mechanistic level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromosomes / genetics
  • Female
  • Germ Cells* / growth & development
  • Germ Cells* / metabolism
  • Homologous Recombination / genetics*
  • Humans
  • Infertility, Male / etiology
  • Infertility, Male / genetics
  • Infertility, Male / metabolism
  • Laminin* / genetics
  • Laminin* / metabolism
  • Male
  • Meiosis / genetics*
  • Mice
  • Mutation
  • Nuclear Lamina* / genetics
  • Nuclear Lamina* / metabolism

Substances

  • Laminin
  • lamin C2

Grants and funding

This work was supported by the German Research Foundation (DFG, http://www.dfg.de), grants Al 1090/1-1 and Al 1090/2-1 (Priority Program 1384 - Mechanisms of genome haploidization) to MA, and the Graduate School GK1048 of the University of Würzburg (http://www.gk-1048.uni-wuerzburg.de). It received further funding by the German Research Foundation (DFG) and the University of Würzburg in the funding programme Open Access Publishing. SO was funded by a grant from the Madrid local Government GR/SAL/0206/2005. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.