Control of neurulation by the nucleosome assembly protein-1-like 2

Neurulation is a complex process of histogenesis involving the precise temp oral and spatial organization of gene expression(1,2) Genes influencing neu rulation include proneural genes determining primary cell fate, neurogenic genes involved in lateral inhibition pathways and genes controlling the fre quency of mitotic events. This is reflected in the aetiology and genetics o f human and mouse neural tube defects, which are of both multifactorial and multigenic origin(3). The X-linked gene Nap1l2, specifically expressed in neurons, encodes a protein that is highly similar to the nucleosome assembl y (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 ov erproduction of neuronal precursor cells. Protein expression studies showed that the Nap1l2 protein binds to condensing chromatin during S phase and i n apoptotic cells, but remained cytoplasmic during G1 phase. Nap1l2 therefo re likely represents a class of tissue-specific factors interacting with ch romatin to regulate neuronal cell proliferation.