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HP1-β is required for development of the cerebral neocortex and neuromuscular junctions
- Source :
- The Journal of Cell Biology, Aucott, R, Bullwinkel, J, Yu, Y, Shi, W, Billur, M, Brown, J P, Menzel, U, Kioussis, D, Wang, G, Reisert, I, Weimer, J, Pandita, R K, Sharma, G G, Pandita, T K, Fundele, R & Singh, P B 2008, ' HP1-beta is required for development of the cerebral neocortex and neuromuscular junctions ', Journal of Cell Biology, vol. 183, no. 4, pp. 597-606 . https://doi.org/10.1083/jcb.200804041
- Publication Year :
- 2008
- Publisher :
- The Rockefeller University Press, 2008.
-
Abstract
- 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.
- Subjects :
- Programmed cell death
Chromosomal Proteins, Non-Histone
Mutant
Diaphragm
Neocortex
Biology
Motor Endplate
Genomic Instability
03 medical and health sciences
Mice
0302 clinical medicine
Report
Heterochromatin
medicine
Animals
Humans
Heterochromatin organization
Research Articles
030304 developmental biology
Genetics
Mice, Knockout
0303 health sciences
Cell Biology
Null allele
3. Good health
Cell biology
Chromatin
medicine.anatomical_structure
Cerebral cortex
Chromobox Protein Homolog 5
Heterochromatin protein 1
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 183
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....796a9f2d7590c1929c5d983e42a3645c