title: Cockayne syndrome b maintains neural precursor function.
abstract: Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS). The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair. CSB also plays a role in chromatin remodeling and mitochondrial function. The role of CSB in neural development is poorly understood. Here we report that the abundance of neural progenitors is normal in Csb(-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb(-/-) and wild type mice. Both embryonic and adult Csb(-/-) neural precursors exhibited defective self-renewal in the neurosphere assay. In Csb(-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres. The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage. Although Csb(-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m(2)) in vitro, neurons differentiated in vitro from Csb(-/-) neural precursors that had been irradiated with 1J/m(2) UV exhibited defective neurite outgrowth. These findings identify a function for Csb in neural precursors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Sacco
authors.forename: Laura
authors.initials: L
authors.lastname: Tamblyn
authors.forename: Nishani
authors.initials: N
authors.lastname: Rajakulendran
authors.forename: Fernando N
authors.initials: FN
authors.lastname: Bralha
authors.forename: Vincent
authors.initials: V
authors.lastname: Tropepe
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Laposa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D049109:Cell Proliferation; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000235:genetics*; D004805:Ependyma / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology* / Q000528:radiation effects; D055495:Neurogenesis / Q000235:genetics / Q000528:radiation effects; D000075223:Poly-ADP-Ribose Binding Proteins; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes