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.