Neural crest cell motility in valproic acid

Fuller, Leah C; Cornelius, Shannon K; Murphy, Charles W; Wiens, Darrell J

doi:10.1016/s0890-6238(02)00059-x

Cited by 51Pharmacological Effects and Toxicity StudiesDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

Neural crest cell motility in valproic acid

Fuller, Leah C, Cornelius, Shannon K, Murphy, Charles W, Wiens, Darrell J·2002·Reproductive Toxicology

DOI 10.1016/s0890-6238(02)00059-x

Open this paper in CoChat — free account

Abstract

Neural crest cells (NCCs) exit the dorsal neural tube and migrate to sites where they form diverse tissues. Valproic acid (VPA) is an anticonvulsant drug that induces neural tube and related defects. Altered NCC migration and proliferation have been proposed as mechanisms of teratogenicity. We cultured neural tube segments from chick embryos in 0.75-3.0mM VPA. We used image analysis, proliferation assays, and fluorescence localization to investigate NCCs during VPA exposure. VPA inhibited attachment of explants and the number that produced migrating cells. VPA markedly decreased the proportion of cells migrating individually, promoting migration as epithelial sheets. VPA at 3mM decreased cellular spreading. Area and perimeter change per minute were reduced, but migration velocity was not. VPA at 2mM reduced proliferation 11% and 3mM arrested proliferation. Immunostaining of VPA-exposed explants revealed N-cadherin-positive cell boundaries within sheets, but independent NCCs did not stain. F-actin staining was reduced in independent NCCs. The data support a VPA mechanism involving interference with epithelial-mesenchymal transition.

Integrity signals

Registry

Crossref · 10.1016/s0890-6238(02)00059-x

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Animal models demonstrate that exposure to valproate impacts short- and long-term neurodevelopmental trajectories, interfering with neural migration pathways at critical points during embryonic development, and potentially contributing to neural tube defects.
“Animal models demonstrate that exposure to valproate impacts both short- and long-term neurodevelopmental trajectories, interfering with neural migration pathways at critical points during embryonic development, and potentially contributing to neural tube defects [126, 127].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [127]

A series of normal stages in the development of the chick embryo
Hamburger, V., & Hamilton, H. L. (1951) · Journal of Morphology · doi:10.1002/jmor.1050880104 · Cited by 12,254 · see citing works
Regulation of Cell Motility by Mitogen-activated Protein Kinase
Klemke, R. L., Cai, S., Giannini, A. L. M., Gallagher, P. J., de Lanerolle, P., & Cheresh, D. A. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.2.481 · Cited by 1,235 · see citing works
Neural Crest Cells Contribute to Normal Aorticopulmonary Septation
Kirby, M. L., Gale, T. F., & Stewart, D. E. (1983) · Science · doi:10.1126/science.6844926 · Cited by 1,118 · see citing works
Regulation of Cadherin Adhesive Activity
Gumbiner, B. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.148.3.399 · Cited by 787 · see citing works
Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects
Milunsky, A. (1989) · JAMA · doi:10.1001/jama.262.20.2847 · Cited by 627 · see citing works
Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin
Witke, W., Sharpe, A. H., Hartwig, J. H., Azuma, T., Stossel, T. P., & Kwiatkowski, D. J. (1995) · Cell · doi:10.1016/0092-8674(95)90369-0 · Cited by 431 · see citing works
Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid
Rosenquist, T. H., Ratashak, S. A., & Selhub, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.26.15227 · Cited by 379 · see citing works
Neural crest cell-cell adhesion controlled by sequential and subpopulationspecific expression of novel cadherins
Nakagawa, S., & Takeichi, M. (1995) · Development · doi:10.1242/dev.121.5.1321 · Cited by 372 · see citing works
Neural-Tube Defects and Derangement of Homocysteine Metabolism
Steegers‐Theunissen, R. P. M., Boers, G. H. J., Trijbels, F. J. M., et al. (1991) · New England Journal of Medicine · doi:10.1056/nejm199101173240315 · Cited by 287 · see citing works
Neural tube defects: A review of human and animal studies on the etiology of neural tube defects
Campbell, L. R., Dayton, D., & Sohal, G. S. (1986) · Teratology · doi:10.1002/tera.1420340206 · Cited by 251 · see citing works
Epithelium-Mesenchyme Transition during Neural Crest Development
Duband, J., Monier, F., Delannet, M., & Newgreen, D. F. (1995) · Cells Tissues Organs · doi:10.1159/000147752 · Cited by 249 · see citing works
Expression of cell adhesion molecules during initiation and cessation of neural crest cell migration
Akitaya, T., & Bronner-Fraser, M. E. (1992) · Developmental Dynamics · doi:10.1002/aja.1001940103 · Cited by 188 · see citing works
The Role of Cell-Cell and Cell-Matrix Interactions in the Morphogenesis of the Neural Crest
Erickson, C. A., & Perris, R. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1221 · Cited by 170 · see citing works
Spatial and temporal distribution of the adherens-junction-associated adhesion molecule A-CAM during avian embryogenesis
Duband, J., Volberg, T., Sabanay, I., et al. (1988) · Development · doi:10.1242/dev.103.2.325 · Cited by 163 · see citing works
Cross Talk between Adhesion Molecules: Control of N-cadherin Activity by Intracellular Signals Elicited by β1 and β3 Integrins in Migrating Neural Crest Cells
Monier-Gavelle, F., & Duband, J. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.7.1663 · Cited by 156 · see citing works
A cell-type-specific abnormality of cell proliferation in mutant (curly tail) mouse embryos developing spinal neural tube defects
Copp, A. J., Brook, F. A., & Roberts, H. J. (1988) · Development · doi:10.1242/dev.104.2.285 · Cited by 142 · see citing works
Homocysteine signal cascade: production of phospholipids, activation of protein kinase C, and the induction of c‐fos and c‐myb in smooth muscle cells
Dalton, M. L., Gadson, P. F., Wrenn, R. W., & Rosenquist, T. H. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.8.9240971 · Cited by 128 · see citing works
Methionine but Not Folinic Acid or Vitamin B-12 Alters the Frequency of Neural Tube Defects in Axd Mutant Mice
Essien, F. B., & Wannberg, S. (1993) · Journal of Nutrition · doi:10.1093/jn/123.1.27 · Cited by 119 · see citing works
5 Neural Crest Development: The Interplay between Morphogenesis and Cell Differentiation
Erickson, C. A., & Reedy, M. V. (1998) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(08)60367-1 · Cited by 113 · see citing works
Methionine and neural tube closure in cultured rat embryos: Morphological and biochemical analyses
Coelho, C. N. D., & Klein, N. W. (1990) · Teratology · doi:10.1002/tera.1420420412 · Cited by 111 · see citing works
Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: Implications for perinatal morbidity and mortality, and for sudden infant death syndrome
Slotkin, T. A., Saleh, J. L., McCook, E. C., & Seidler, F. J. (1997) · Teratology · doi:10.1002/(sici)1096-9926(199703)55:3 · Cited by 111 · see citing works
Folic Acid Metabolism and Mechanisms of Neural Tube Defects
Scott, J. M., Weir, D. G., Molloy, A. M., et al. (2007) · Novartis Foundation symposium · doi:10.1002/9780470514559.ch11 · Cited by 110 · see citing works
open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord
Günther, T., Struwe, M., Aguzzi, A., & Schughart, K. (1994) · Development · doi:10.1242/dev.120.11.3119 · Cited by 101 · see citing works
Valproic acid-induced neural tube defects: Reduction by folinic acid in the mouse
Trotz, M., Wegner, C., & Nau, H. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90562-5 · Cited by 95 · see citing works
Control of Epitheliomesenchymal Transformation. I. Events in the Onset of Neural Crest Cell Migration Are Separable and Inducible by Protein Kinase Inhibitors
Newgreen, D. F., & Minichiello, J. (1995) · Developmental Biology · doi:10.1006/dbio.1995.1198 · Cited by 88 · see citing works
Antitumor activity of sodium valproate in cultures of human neuroblastoma cells
Cínatl, J., Činátl, J., Scholz, M., et al. (1996) · Anti-Cancer Drugs · doi:10.1097/00001813-199609000-00008 · Cited by 88 · see citing works
Transfer of valproic acid and its main active unsaturated metabolite to the gestational tissue: Correlation with neural tube defect formation in the mouse
Nau, H. (1986) · Teratology · doi:10.1002/tera.1420330105 · Cited by 87 · see citing works
NuMA is a component of an insoluble matrix at mitotic spindle poles
Dionne, M. A., Howard, L., & Compton, D. A. (1999) · Cell Motility and the Cytoskeleton · doi:10.1002/(sici)1097-0169(1999)42:3 · Cited by 81 · see citing works
Delayed neural crest cell emigration from Sp and Spd mouse neural tube explants
Moase, C. E., & Trasler, D. G. (1990) · Teratology · doi:10.1002/tera.1420420208 · Cited by 80 · see citing works
N-CAM alterations in splotch neural tube defect mouse embryos
Moase, C. E., & Trasler, D. G. (1991) · Development · doi:10.1242/dev.113.3.1049 · Cited by 79 · see citing works
Control of N-cadherin-mediated intercellular adhesion in migrating neural crest cells in vitro
Monier-Gavelle, F., & Duband, J. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.12.3839 · Cited by 73 · see citing works
The Role of Nutrition in Neural Tube Defects
Scott, J. M., Kirke, P. N., & Weir, D. G. (1990) · Annual Review of Nutrition · doi:10.1146/annurev.nu.10.070190.001425 · Cited by 71 · see citing works
Valproic Acid‐Induced Neural Tube Defects
Nau, H. (2007) · Novartis Foundation symposium · doi:10.1002/9780470514559.ch9 · Cited by 66 · see citing works
Cleavage of A-CAM by endogenous proteinases in cultured lens cells and in developing chick embryos
Volk, T., Volberg, T., Sabanay, I., et al. (1990) · Developmental Biology · doi:10.1016/0012-1606(90)90301-x · Cited by 62 · see citing works
Smooth muscle cells of neural crest origin form the aorticopulmonary septum in the avian embryo
Beall, A. C., & Rosenquist, T. H. (1990) · The Anatomical Record · doi:10.1002/ar.1092260313 · Cited by 58 · see citing works
The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid-G1 phase
Martin, M. L., & Regan, M. (1991) · Brain Research · doi:10.1016/0006-8993(91)90193-y · Cited by 55 · see citing works
Control of Epitheliomesenchymal Transformation
Newgreen, D. F., & Minichiello, J. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0135 · Cited by 48 · see citing works
VPA-induced neural tube defects in mice. I. altered metabolism of sulfur amino acids and glutathione
Hishida, R., & Nau, H. (1998) · Teratogenesis Carcinogenesis and Mutagenesis · doi:10.1002/(sici)1520-6866(1998)18:2 · Cited by 43 · see citing works
Growth factor action in neural crest cell diversification
Sieber‐Blum, M., & Zhang, J. M. (1997) · Journal of Anatomy · doi:10.1046/j.1469-7580.1997.19140493.x · Cited by 41 · see citing works
In vitro microtubule-based organelle transport in wild-typeDictyostelium and cells overexpressing a truncated dynein heavy chain
Pollock, N., Koonce, M. P., de Hostos, E. L., & Vale, R. D. (1998) · Cell Motility and the Cytoskeleton · doi:10.1002/(sici)1097-0169(1998)40:3 · Cited by 37 · see citing works
Valproic acid-induced alterations in growth and neurotrophic factor
Bennett, G. D., Wlodarczyk, B. J., Calvin, J. A., Craig, J. C., & Finnell, R. H. (2000) · Reproductive Toxicology · doi:10.1016/s0890-6238(99)00064-7 · Cited by 36 · see citing works
Relationship between valproic acid dosage, plasma concentration and clearance in adult monotherapy patients with epilepsy
Gidal, B. E., Pitterle, M. E., Spencer, N. W., et al. (1995) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.1995.tb00651.x · Cited by 36 · see citing works
Development of the musculoelastic septation complex in the avian truncus arteriosus
Rosenquist, T. H., Fray‐Gavalas, C., Waldo, K. L., et al. (1990) · American Journal of Anatomy · doi:10.1002/aja.1001890406 · Cited by 31 · see citing works
Cytoskeletal changes during neurogenesis in cultures of avian neural crest cells
Haendel, M. A., Bollinger, K. E., & Baas, P. W. (1996) · Journal of Neurocytology · doi:10.1007/bf02284803 · Cited by 27 · see citing works
Validation of an in Vitro Teratology System Using Chiral Substances: Stereoselective Teratogenicity of 4-yn-Valproic Acid in Cultured Mouse Embryos
Andrews, J. E., Ebron‐McCoy, M. T., Bojic, U., et al. (1995) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1995.1112 · Cited by 25 · see citing works
Early heart development in the chick embryo: effects of isotretinoin on cell proliferation, α-actin synthesis, and development of contractions
Wiens, D. J., Mann, T. K., Fedderson, D. E., Rathmell, W. K., & Franck, B. H. (1992) · Differentiation · doi:10.1111/j.1432-0436.1992.tb00686.x · Cited by 24 · see citing works
Self-citation
Teratogenic potency of valproate analogues evaluated by quantitative estimation of cellular morphology in vitro
Berezin, V., Kawa, A., Bojic, U., et al. (1996) · Toxicology in Vitro · doi:10.1016/s0887-2333(96)00049-5 · Cited by 19 · see citing works
Effect of Ovarian Steroids on Maintenance of Pregnancy in Rats Fed Diets Devoid of One Essential Amino Acid
NIIYAMA, Y., Kishi, K., & INOUE, G. (1970) · Journal of Nutrition · doi:10.1093/jn/100.12.1461 · Cited by 15 · see citing works
In vitro neuroteratogenicity of valproic acid and 4-en-VPA
Gofflot, F., Nassogne, M., Etzion, T., et al. (1995) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(94)00094-t · Cited by 14 · see citing works
Valproic Acid Teratogenesis and Embryonic Lipid Metabolism
Clarke, D. O., & Brown, N. A. (1987) · Springer eBooks · doi:10.1007/978-3-642-72558-6_20 · Cited by 13 · see citing works
Spatial and temporal distribution of vinculin and talin in migrating avian neural crest cells and their derivatives
Duband, J., & Thiery, J. P. (1990) · Development · doi:10.1242/dev.108.3.421 · Cited by 13 · see citing works
Zinc concentrations in mouse embryo and maternal plasma
Wegner, C., Drews, E., & Nau, H. (1990) · Biological Trace Element Research · doi:10.1007/bf02990416 · Cited by 13 · see citing works
Isotretinoin alters morphology, polarity, and motility of neural crest cells in culture
Orris, A. S. (1999) · Reproductive Toxicology · doi:10.1016/s0890-6238(98)00059-8 · Cited by 3 · see citing works

Flagged first, then by citations

Sorted by citations

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797 · see citing works
The contribution of environmental exposure to the etiology of autism spectrum disorder
Bölte, S., Girdler, S., & Marschik, P. B. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2988-4 · Cited by 509 · see citing works

The neural border: Induction, specification and maturation of the territory that generates neural crest cells
Pla, P., & Monsoro-Burq, A. H. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.05.018 · Cited by 115 · see citing works
The Timing of Appearance and Pathway of Migration of Cranial Neural Crest‐derived Precursors of Melanocytes in Chick Embryos
Takiguchi‐Hayashi, K., & Kitamura, K. (1993) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.1993.00173.x · Cited by 4 · see citing works
Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study
Turgut, Ü. K., Kazan, S., Çakın, H., et al. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.05.008 · Cited by 14 · see citing works
A critical role for Cadherin6B in regulating avian neural crest emigration
Coles, E. G., Taneyhill, L. A., & Bronner-Fraser, M. E. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.09.056 · Cited by 127 · see citing works
Evidence for dynamic rearrangements but lack of fate or position
McKinney, M. C., Fukatsu, K., Morrison, J., et al. (2013) · The FASEB Journal · doi:10.1096/fasebj.27.1_supplement.965.1

Authors: Fuller, L. C., Cornelius, S. K., Murphy, C. W., & Wiens, D. J.
Affiliations: University of Northern Iowa (US)
Corresponding author: Wiens, Darrell J
Venue: Reproductive Toxicology
Publisher: Elsevier BV
Published: 2002-11
Volume: 16
Issue: 6
Pages: 825-839
ISSN: 0890-6238 (ISSN-L)
DOI: 10.1016/s0890-6238(02)00059-x
OpenAlex: W2034890342
Cited by: 51
References: 53
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 8 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 2
FWCI: 0.60
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Reproductive Toxicology (publishedVersion)
PubMed (publishedVersion)
UNI ScholarWorks (University of Northern Iowa) (submittedVersion)
Funders: American Heart Association
University of Northern Iowa
National Institutes of Health
Directorate for Biological Sciences
National Institute of Child Health and Human Development
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: neural crest cells, valproic acid, teratogenicity, neural tube defects, cell migration, cell proliferation, epithelial-mesenchymal transition, N-cadherin, F-actin
MeSH terms: Animals, Anticonvulsants, Bromodeoxyuridine, Cell Division, Cell Movement, Chick Embryo, Cytoskeleton, Dose-Response Relationship, Drug, Drug Antagonism, Drug Combinations, Folic Acid, Image Processing, Computer-Assisted, Intercellular Junctions, Microscopy, Fluorescence, Neural Crest, Organ Culture Techniques, Valproic Acid, Microscopy, Video

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Neural crest cell motility in valproic acid

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks