Apparent lability of neural tube closure in laboratory animals and humans

DeSesso, John M.; Scialli, Anthony R.; Holson, Joseph F.

doi:10.1002/(sici)1096-8628(19991119)87:2<143::aid-ajmg6>3.0.co;2-j

Cited by 56 publications

(32 citation statements)

References 97 publications

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“…Past experiments directly support these predictions (e.g., Smith and Schoenwolf, 1991). Consequently, the hinge point model has gained wide acceptance (e.g., Fleming et al, 1997;DeSesso et al, 1999;Harris and Juriloff, 1999;Gilbert, 2000;Kalthoff, 2001). …”

Section: The Developmental Dynamics Of Neurulation Synergistic Roles mentioning

confidence: 96%

“…NTDs, such as anencephaly (e.g., encephalocele) and spina bifida (e.g., myelomeningocele), are associated with substantial human morbidity and mortality, and they result in significant fetal wastage. NTDs are among the most common birth defects present in newborn humans (as high as 1:500 births in USA; reviewed by Copp et al, 1990;DeSesso et al, 1999;Harris and Juriloff, 1999). It is clear from a wealth of genetic and clinical data that an individual's liability to form a neural tube defect has both a genetic and environmental cause.…”

Section: Genetic Control Of Neurulation Increases Its Efficiency and mentioning

confidence: 99%

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Towards a cellular and molecular understanding of neurulation

Colas

Schoenwolf

2001

Developmental Dynamics

400

376

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Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system. The goal of studies on neurulation is to understand its tissue, cellular and molecular basis, as well as how neurulation is perturbed during the formation of neural tube defects. The tissue basis of neurulation consists of a series of coordinated morphogenetic movements within the primitive streak (e.g., regression of Hensen's node) and nascent primary germ layers formed during gastrulation. Signaling occurs between Hensen's node and the nascent ectoderm, initiating neurulation by inducing the neural plate (i.e., actually, by suppressing development of the epidermal ectoderm). Tissue movements subsequently result in shaping and bending of the neural plate and closure of the neural groove. The cellular basis of the tissue movements of neurulation consists of changes in the behavior of the constituent cells; namely, changes in cell number, position, shape, size and adhesion. Neurulation, like any morphogenetic event, occurs within the milieu of generic biophysical determinants of form present in all living tissues. Such forces govern and to some degree control morphogenesis in a tissue-autonomous manner. The molecular basis of neurulation remains largely unknown, but we suggest that neurulation genes have evolved to work in concert with such determinants, so that appropriate changes occur in the behaviors of the correct populations of cells at the correct time, maximizing the efficiency of neurulation and leading to heritable speciesand axial-differences in this process. In this article, we review the tissue and cellular basis of neurulation and provide strategies to determine its molecular basis. We expect that such strategies will lead to the identification in the near future of critical neurulation genes, genes that when mutated perturb neurulation in a highly specific and predictable fashion and cause neurulation defects, thereby contributing to the formation of neural tube defects.

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Section: The Developmental Dynamics Of Neurulation Synergistic Roles mentioning

confidence: 96%

Section: Genetic Control Of Neurulation Increases Its Efficiency and mentioning

confidence: 99%

Towards a cellular and molecular understanding of neurulation

Colas

Schoenwolf

2001

Developmental Dynamics

400

376

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“…Neural tube defects (NTDs) are among the most prevalent and disabling of all the congenital malformations, with as many as 10-20 infants per 10,000 births being affected (DeSesso et al 1999). NTDs are major malformations of the central nervous system, in which the canal of the malformed brain or spinal cord is persistently open to the outside environment, resulting in anencephaly cranially and spina bifida caudally.…”

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confidence: 99%

“…A multifactorial model for NTD etiology has been proposed where susceptible genotypes are affected by a number of extrinsic factors such as maternal age, nutrition, socioeconomic influence, and exposure to NTDinducing toxicants or drugs during pregnancy (Ehlers et al, 1996;DeSesso et al, 1999). The antiepileptic drug valproic acid (VA) has been implicated as a human teratogen in both retrospective and prospective studies.…”

mentioning

confidence: 99%

Valproic acid‐induced fetal malformations are reduced by maternal immune stimulation with granulocyte‐macrophage colony‐stimulating factor or interferon‐γ

Hrubec

Yan

et al. 2006

Anat. Rec.

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Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly or anencephaly, as well as spina bifida. In mice, nonspecific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes-induced NTDs. We hypothesized that nonspecific activation of the maternal immune system with interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce valproic acid (VA)-induced defects as well. Female CD-1 mice were given immune stimulant prebreeding: either IFN-g or GM-CSF. Approximately half of the control and immune-stimulated pregnant females were then exposed to 500 mg/kg VA on the morning of gestational day 8. The incidence of developmental defects was determined on gestational day 17 from at least eight litters in each of the following treatment groups: control, VA only, IFN-g only, IFN-g þ VA, GM-CSF only, and GM-CSF þ VA. The incidence of NTDs was 18% in fetuses exposed to VA alone, compared to 3.7% and 2.9% in fetuses exposed to IFN-g þ VA, or GM-CSF þ VA respectively. Ocular defects were also significantly reduced from 28.0% in VA exposed groups to 9.8% in IFN-g þ VA and 12.5% in GM-CSF þ VA groups. The mechanisms by which maternal immune stimulation prevents birth defects remain unclear, but may involve maternal or fetal production of cytokines or growth factors which protect the fetus from the dysregulatory effects of teratogens. Anat

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“…spina bifida ͉ neural development ͉ apoptosis ͉ caspase ͉ cell death N eural tube closure defects account for a significant portion of the congenital malformations that affect humans (1). Such defects include spina bifida, exencephaly, cranioschisis, and hydrocephaly.…”

mentioning

confidence: 99%

Apaf-1 deficiency and neural tube closure defects are found in fog mice

Honarpour

Gilbert

Lahn

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The forebrain overgrowth mutation ( fog) was originally described as a spontaneous autosomal recessive mutation mapping to mouse chromosome 10 that produces forebrain defects, facial defects, and spina bifida. Although the fog mutant has been characterized and available to investigators for several years, the underlying mutation causing the pathology has not been known. Because of its phenotypic resemblance to apoptotic protease activating factor-1 (Apaf-1) knockout mice, we have investigated the possibility that the fog mutation is in the Apaf-1 gene. Allelic complementation, Western blot analysis, and caspase activation assays indicate that fog mutant mice lack Apaf-1 activity. Northern blot and reverse transcription-PCR analysis show that Apaf-1 mRNA is aberrantly processed, resulting in greatly reduced expression levels of normal Apaf-1 mRNA. These findings are strongly suggestive of the fog mutation being a hypomorphic Apaf-1 defect and implicate neural progenitor cell death in the pathogenesis of spina bifida-a common human congenital malformation. Because a complete deficiency in Apaf-1 usually results in perinatal lethality and fog͞fog mice more readily survive into adulthood, these mutants serve as a valuable model with which apoptotic cell death can be studied in vivo.spina bifida ͉ neural development ͉ apoptosis ͉ caspase ͉ cell death N eural tube closure defects account for a significant portion of the congenital malformations that affect humans (1). Such defects include spina bifida, exencephaly, cranioschisis, and hydrocephaly. The cause and inheritance of these defects are complex, reflecting the complex developmental events required for neural tube formation and closure.Neural plate formation, neural fold elevation, neural tube closure, and neural crest cell migration are just a few of the operations that are tightly regulated during neurulation. Many mouse models have been used to study neural tube defects (2). The mutants studied have either arisen spontaneously or have been generated by using targeted gene disruption. One such mouse model is the forebrain overgrowth ( fog) mutant, which has a spontaneous mutation in an uncharacterized gene and is transmitted in an autosomal recessive manner (3).Apoptotic cell death has been shown to play a critical role in neurogenesis. Specifically, proteins required for the cytochromec-mediated apoptotic pathway [such as apoptotic protease activating factor-1 (Apaf-1), caspase-9, and caspase-3] are important for neural tube closure in vivo (4-9). In this biochemical cascade, cytochrome c released from the mitochondria is recruited to Apaf-1. In the presence of dATP, the cytochrome-c͞Apaf-1 complex is able to procure and promote activation of procaspase-9 to caspase-9. The activation of caspase-9 then results in the subsequent activation of caspase-3, a terminal event in apoptotic cell death. In mice, Apaf-1 deficiency results in a dramatic elevation in the number of neural progenitor cells resulting in the thickening of the neuroepithelium (9). Because morph...

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Apparent lability of neural tube closure in laboratory animals and humans

Cited by 56 publications

References 97 publications

Towards a cellular and molecular understanding of neurulation

Towards a cellular and molecular understanding of neurulation

Valproic acid‐induced fetal malformations are reduced by maternal immune stimulation with granulocyte‐macrophage colony‐stimulating factor or interferon‐γ

Apaf-1 deficiency and neural tube closure defects are found in fog mice

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