Severe Neural Tube Defects Research Articles

Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord.

We describe a new mouse mutation, designated open brain (opb), which results in severe defects in the developing neural tube. Homozygous opb embryos exhibited an exencephalic malformation involving the forebrain, midbrain and hindbrain regions. The primary defect of the exencephaly could be traced back to a failure to initiate neural tube closure at the midbrain-forebrain boundary. Severe malformations in the spinal cord and dorsal root ganglia were observed in the thoracic region. The spinal cord of opb mutant embryos exhibited an abnormal circular to oval shape and showed defects in both ventral and dorsal regions. In severely affected spinal cord regions, a dorsalmost region of cells negative for Wnt-3a, Msx-2, Pax-3 and Pax-6 gene expression was detected and dorsal expression of Pax-6 was increased. In ventral regions, the area of Shh and HNF-3 beta expression was enlarged and the future motor neuron horns appeared to be reduced in size. These observations indicate that opb embryos exhibit defects in the specification of cells along the dorsoventral axis of the developing spinal cord. Although small dorsal root ganglia were formed in opb mutants, their metameric organization was lost. In addition, defects in eye development and malformations in the axial skeleton and developing limbs were observed. The implications of these findings are discussed in the context of dorsoventral patterning of the developing neural tube and compared with known mouse mutants exhibiting similar defects.

Developmental Basis of Severe Neural Tube Defects in the loop-tail (Lp) Mutant Mouse: Use of Microsatellite DNA Markers to Identify Embryonic Genotype

Mouse embryos homozygous for the mutation loop-tail (Lp) develop lethal defects in which the neural tube remains open from the hindbrain to the caudal extremity, a condition that closely resembles the human malformation craniorachischisis. Heterozygotes develop tail defects and occasional spina bifida, but are generally viable. In order to study the early development of these defects, it is necessary to determine the genotype of embryos at stages prior to the first appearance of the morphological abnormalities. We used a microsatellite DNA sequence, Crp, that is closely linked to the Lp locus and which segregates polymorphic variants in matings between Lp/+ mice, thus permitting identification of embryos of Lp/Lp, Lp/+ and +/+ genotypes. We found that the severe phenotype craniorachischisis is present at 9.5 and 10.5 days of gestation only in Lp/Lp embryos in utero, whereas Lp/+ and +/+ littermates show neural tube closure throughout most of the body axis. The open neural tube phenotype also develops in Lp/Lp embryos growing in whole embryo culture. A small proportion of Lp/+ embryos were found to develop this phenotype in vitro, but only when culture conditions were suboptimal. Analysis of 8.5-day embryos revealed that the initial defect in Lp/Lp embryos is failure to initiate neural tube closure at the cervical/hindbrain boundary when the embryo has 6-7 somites. Thereafter, the neural tube remains open throughout the body axis, with the exception of the midbrain and forebrain where neural tube closure is initiated independently. Closure at the midbrain/forebrain boundary does not appear to be defective in Lp/Lp embryos. Heterozygous Lp/+ embryos initiate neural tube closure at the cervical/hindbrain boundary with a slight delay compared with +/+ littermates. Moreover, at 10.5 days of gestation, Lp/+ embryos undergo delayed closure of the posterior neuropore. Thus, Lp/+ embryos are defective in several aspects of the neurulation process. The pattern of delayed neuropore closure in Lp/+ embryos resembles that caused by the ct and Sp mutations and is likely to be responsible for the development of tail defects (i.e., looped tails) and spina bifida in Lp/+ mice. The use of microsatellite markers to determine the genotype of mutant embryos has general application: microsatellites are widespread throughout the mouse genome, so that informative sequences are likely to be available with close linkage to the majority of mutant genes. Moreover, polymorphisms can be detected using the polymerase chain reaction, making it possible to determine the genotype of very early embryos when only small amounts of material are available.

Fetal Neurosurgery

Advances in antenatal diagnostic techniques coupled with innovative neurosurgical techniques have led to the consideration of treatment of major congenital neurological anomalies in utero. The rationale for such fetal neurosurgical intervention rests in the possibility of halting the progressive neurological deterioration and ameliorating the sequelae associated with severe congenital hydrocephalus and neural tube defects. Although the concept of in utero treatment of neurological anomalies remains more theoretical and experimental than clinically practical, preliminary evidence from both the laboratory and the clinic has begun to emerge to support continued efforts in this field. This review focuses on the role of neurosurgeons in surgery in utero. Emphasis is placed on advances in antenatal diagnosis, current research in surgery in utero, and potential clinical applications of fetal neurosurgery.

Two Additional Cases of Lumbar Malformation From the Peruvian Coastal Preceramic

Previous articleNext article No AccessResearch ConclusionsTwo Additional Cases of Lumbar Malformation From the Peruvian Coastal PreceramicRobert A. FeldmanRobert A. Feldman Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Current Anthropology Volume 22, Number 3Jun., 1981 Sponsored by the Wenner-Gren Foundation for Anthropological Research Article DOIhttps://doi.org/10.1086/202666 Views: 4Total views on this site Citations: 2Citations are reported from Crossref Copyright 1981 The Wenner-Gren Foundation for Anthropological ResearchPDF download Crossref reports the following articles citing this article:D. N. Dickel, G. H. Doran Severe neural tube defect syndrome from the early archaic of Florida, American Journal of Physical Anthropology 80, no.33 (Nov 1989): 325–334.https://doi.org/10.1002/ajpa.1330800306Robert T. Anderson An orthopedic ethnography in Rural Nepal, Medical Anthropology 8, no.11 (May 2010): 46–59.https://doi.org/10.1080/01459740.1984.9965888

Maternal serum alpha-fetoprotein screening in a provincial Health District.

Maternal serum alpha-fetoprotein (AFP) estimation as a routine screening test for neural tube defect (NTD) was introduced into the West Berkshire Health District, where 17 per cent of all deliveries and most of the antenatal care is undertaken by the general practitioners. In the first year, 4458 patients were screened and 43 of those (0.96 per cent) had raised serum AFP levels. Amniocentesis was performed on 31 patients (0.69 per cent). Ten fetuses with severe NTDs and one with exomphalos were detected and the pregnancies terminated. In six patients, raised serum AFP levels were due to fetal death. No normal pregnancy was terminated. Acceptability by patients was high. Provided that a good diagnostic ultrasound facility is available locally, maternal serum AFP estimation seemed to be a valuable screening test.

Prenatal diagnosis of a neural tube defect: Meckel syndrome.

A severe neural tube defect diagnosed in a 191/2-week-old "at risk" fetus on the evidence of a markedly elevated alpha-fetoprotein level in the amniotic fluid, turned out to be an occipital myelocoele. However, the fetus also had polycystic kidneys and postaxial hexadactyly on all extremities. The karyotype was normal. These are the features of the rare Meckel syndrome, caused by a pleiotropic, autosomal, recessive gene, and one and possibly two other sibs were also affected.

Alpha-Fetoprotein Levels in Amniotic Fluids from Spontaneous Abortions

Alpha-fetoprotein (A.F.P.) levels in the amniotic fluid were determined in 54 cases of spontaneous abortion in which the amniotic sac remained intact. These levels were correlated with the morphological and cytogenetic status of the fetus. Of the 29 fetuses with no apparent abnormality 22 had A.F.P. levels below 50 mug/ml, while 10 of the 11 fetuses with severe neural tube defects had raised levels (50-305 mu/ml). Seventeen fetuses had chromosome anomalies of various types. Three out of four which were 45, X had considerably raised A.F.P. levels (78-210 mug/ml) but fetuses with other chromosome constitutions and no neural tube defects had levels no higher than 32 mug/ml.

MATERNAL SERUM-ALPHA-FETOPROTEIN LEVELS AND PRENATAL DIAGNOSIS OF NEURAL-TUBE DEFECTS

Maternal serum-alpha-fetoprotein (A.F.P.) levels were compared throughout pregnancy in women bearing fetuses with severe neural-tube defects and in control women. From the second trimester onwards, the former group had higher levels than the controls, but the difference was not always clear-cut, rendering such a test less reliable than assay of the amniotic-fluid A.F.P. The blood-A.F.P. levels of seven anencephalic fetuses were normal for their gestational age, suggesting that there is no increased synthesis of A.F.P. in fetuses with severe neural-tube defects.