Gcn5 was the first transcription-related histone acetyltransferase (HAT) to be identified. However, the functions of this enzyme in mammalian cells remain poorly defined. Deletion of Gcn5 in mice leads to early embryonic lethality with increased apoptosis in mesodermal lineages. Here we show that deletion of p53 allows Gcn5(-/-) embryos to survive longer, but Gcn5(-/-) p53(-/-) embryos still di...

Dlx5 and Dlx6 homeobox genes are expressed in developing and mature cortical interneurons. Simultaneous deletion of Dlx5 and 6 results in exencephaly of the anterior brain; despite this defect, prenatal basal ganglia differentiation appeared largely intact, while tangential migration of Lhx6(+) and Mafb(+) interneurons to the cortex was reduced and disordered. The migration deficits were associ...

Proper levels of gene expression are important for normal mammalian development. Typically, altered gene dosage caused by karyotypic abnormalities results in embryonic lethality or birth defects. Segmental aneuploidy can be compatible with life but often results in contiguous gene syndromes. The ability to manipulate the mouse genome allows the systematic exploration of regions that are affecte...

Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme. We demonstrate that Hectd1 is a functional ubiquitin ligase and t...

The primary cilium originates from the mother centriole and participates in critical functions during organogenesis. Defects in cilia biogenesis or function lead to pleiotropic phenotypes. Mutations in centrosome-cilia gene CC2D2A result in Meckel and Joubert syndromes. Here we generate a Cc2d2a(-/-) mouse that recapitulates features of Meckel syndrome including embryonic lethality and multiorg...

Sodium arsenate induces developmental malformations in a variety of experimental animals. In the golden hamster, the intravenous (or intraperitoneal) administration of 20 mg/kg of sodium arsenate during day 8 to 9 of gestation induces a rather specific spectrum of congenital malformations. This period corresponds to the period of very rapid differentiation and major organogenesis in this animal...

Introduction. Acrania is a very rare lethal congenital malformation characterized by an absence of the cranial vault with developed cerebral hemispheres. It sometimes confused anencephaly in which both forebrain and neurocranium are not developed. Although these two conditions principally differ their morphology pathogenesis, acrania may be precursor development through process known as Acrania...

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic devel...

The amnion rupture sequence is a heterogeneous group of congenital deformities in which rupture of the amnion occurs early in gestation. Fragments of the amnion may adhere to, or encircle and constrict, embryonic parts. This may interrupt normal morphogenesis and cause deformity or even mutilation of formed structures; large cranial defects are a common feature. In contrast to other causes of c...