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HP1-β is required for development of the cerebral neocortex and neuromuscular junctions
Correspondence to Prim B. Singh: psingh{at}fz-borstel.de
HP1 proteins are thought to be modulators of chromatin organization in all mammals, yet their exact physiological function remains unknown. In a first attempt to elucidate the function of these proteins in vivo, we disrupted the murine Cbx1 gene, which encodes the HP1-β isotype, and show that the Cbx1–/–-null mutation leads to perinatal lethality. The newborn mice succumbed to acute respiratory failure, whose likely cause is the defective development of neuromuscular junctions within the endplate of the diaphragm. We also observe aberrant cerebral cortex development in Cbx1–/– mutant brains, which have reduced proliferation of neuronal precursors, widespread cell death, and edema. In vitro cultures of neurospheres from Cbx1–/– mutant brains reveal a dramatic genomic instability. Our results demonstrate that HP1 proteins are not functionally redundant and that they are likely to regulate lineage-specific changes in heterochromatin organization.
R. Aucott's present address is Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
J.P. Brown's present address is Children's Hospital Oakland Research Institute, Oakland, CA 94609.
Abbreviations used in this paper: AChR, acetylcholine receptor; CD, chromodomain; CP, cortical plate; CSD, chromoshadow domain; df, degree of freedom; DP, double positive; LCR, locus control region; MEF, murine embryonic fibroblast; NeuN, neuronal nuclei; NF, neurofilament; PCD, premature centromere division; PEV, position-effect variegation; PNA, peptide nucleic acid; SP, subplate; VZ, ventricular zone.
© 2008 Aucott et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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