title: Gene expression profiling identifies eleven DNA repair genes down-regulated during mouse neural crest cell migration.
abstract: Neural Crest Cells (NCCs) are transient multipotent migratory cells that derive from the embryonic neural crest which is itself derived from the margin of the neural tube. DNA repair genes are expressed in the early stages of mammalian development to reduce possible replication errors and genotoxic damage. Some birth defects and cancers are due to inappropriate or defective DNA repair machinery, indicating that the proper functioning of DNA repair genes in the early stages of fetal development is essential for maintaining DNA integrity. We performed a genome-wide expression analysis combining laser capture microdissection (LCM) and high-density oligo-microarray of murine NCCs at pre-migratory embryonic days 8.5 (E8.5), and at E13.5, as well as on neural crest-derived cells from the adrenal medulla at postnatal day 90. We found 11 genes involved in DNA repair activity (response to DNA damage stimulus, DNA damage checkpoint, base-excision repair, mismatch repair), over-expressed in the early stages of mouse embryo development. Expression of these 11 genes was very low or undetectable in the differentiated adrenal medulla of the adult mouse. Amongst the 11 genes, 6 had not been previously reported as being over-expressed during mouse embryonic development. High expression of DNA repair genes in enriched NCCs during early embryonic development may contribute to maintaining DNA integrity whilst failure of some of these genes may be associated with the onset of genetic disease and cancer. Our model of enriched murine NCCs and neural crest-derived cells can be used to elucidate the key roles of genes during normal embryonic development and in cancer pathogenesis.
authors.affiliation: Laboratory of Italian Neuroblastoma Foundation, Genoa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Albino
authors.forename: Antonella
authors.initials: A
authors.lastname: Brizzolara
authors.forename: Stefano
authors.initials: S
authors.lastname: Moretti
authors.forename: Carla
authors.initials: C
authors.lastname: Falugi
authors.forename: Valentina
authors.initials: V
authors.lastname: Mirisola
authors.forename: Paola
authors.initials: P
authors.lastname: Scaruffi
authors.forename: Michele
authors.initials: M
authors.lastname: Di Candia
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.forename: Simona
authors.initials: S
authors.lastname: Coco
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C485953:Rad18 protein, mouse; C498645:Ris2 protein, mouse