Control of neurulation by the nucleosome assembly protein-1-like 2.
Neurulation is a complex process of histogenesis involving the precise temporal and spatial organization of gene expression. Genes influencing neurulation include proneural genes determining primary cell fate, neurogenic genes involved in lateral inhibition pathways and genes controlling the frequency of mitotic events. This is reflected in the aetiology and genetics of human and mouse neural tube defects, which are of both multifactorial and multigenic origin. The X-linked gene Nap1l2, specifically expressed in neurons, encodes a protein that is highly similar to the nucleosome assembly (NAP) and SET proteins. We inactivated Nap1l2 in mice by gene targeting, leading to embryonic lethality from mid-gestation onwards. Surviving mutant chimaeric embryos showed extensive surface ectoderm defects as well as the presence of open neural tubes and exposed brains similar to those observed in human spina bifida and anencephaly. These defects correlated with an overproduction of neuronal precursor cells. Protein expression studies showed that the Nap1l2 protein binds to condensing chromatin during S phase and in apoptotic cells, but remained cytoplasmic during G1 phase. Nap1l2 therefore likely represents a class of tissue-specific factors interacting with chromatin to regulate neuronal cell proliferation.
Rogner
U C
UC
Génétique Moléculaire Murine CNRS URA 1947, Institut Pasteur, Paris Cedex 15, France. urogner@pasteur.fr
Spyropoulos
D D
DD
Le Novère
N
N
Changeux
J P
JP
Avner
P
P
D000818:Animals; D002678:Chimera / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009420:Nervous System / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008164:Luminescent Proteins; C466114:NAP1L2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins