The Continuing Challenge of Understanding, Preventing, and Treating Neural Tube Defects

Wallingford, John B.; Niswander, Lee; Shaw, Gary M.; Finnell, Richard H.

doi:10.1126/science.1222002

Cited by 394 publications

(379 citation statements)

References 104 publications

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“…They result from the failure of the neural tube to close leading to exencephaly or spina bifida (Wallingford et al, 2013). Currently, there is no effective treatment for NTDs once the neural tube has failed to close and, because closure is completed by day 28 of gestation in humans, preventive therapy must be targeted to early pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…In mice, knockout of Folr1 results in an open neural tube by embryonic day 9.5, when heterozygotes or wild-type littermate embryos show a closed neural tube. This phenotype leads to death of homozygous embryos in utero (Finnell et al, 2002;Piedrahita et al, 1999;Spiegelstein et al, 2004;Wallingford et al, 2013). The specific cellular mechanisms dependent on Folr1 during mouse neural tube formation are unclear.…”

Section: Introductionmentioning

confidence: 99%

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Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

2017

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Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

2017

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“…Collective movement occurs in the streaming and slug stages of Dd, to be described later. In other cases, cells remain attached to one another, and movement involves massive, coordinated rearrangements of entire tissues, such as folding of the neural plate to form a tube [5,6]. Movement in both cases involves the same processes as for individual cells, with the addition of more-or-less tight coupling between the movement of neighbouring cells, and we refer to both cases as tissue movement.…”

Section: Introductionmentioning

confidence: 99%

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

2016

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Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.

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“…1 These malformations are common (1/1000 births) and often cause infant mortality. 2 Epidemiological studies indicate that NTDs are caused by complex genetic determinants in combination with environmental factors, both poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The intracellular carboxyl terminal domain of Vangl proteins contains plasma membrane targeting signals

Iliescu

Gros

2014

Protein Science

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Vangl1 and Vangl2 are integral membrane proteins that play a critical role in establishing planar cell polarity (PCP) in epithelial cells and are required for convergent extension (CE) movements during embryogenesis. Their proper targeting to the plasma membrane (PM) is required for function. We created discrete deletions at the amino and carboxy termini of Vangl1 and monitored the effect of the mutations on PM targeting in Madin-Darby canine kidney cells. Our results show that the Vangl1 amino terminus lacks PM targeting determinants, and these are restricted to the carboxy terminus, including the predicted PDZBM motif at the C-terminus.

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The Continuing Challenge of Understanding, Preventing, and Treating Neural Tube Defects

Cited by 394 publications

References 104 publications

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

The intracellular carboxyl terminal domain of Vangl proteins contains plasma membrane targeting signals

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