Article
Cell Biology
John W. Steele, Ying Linda Lin, Nellie Chen, Bogdan J. Wlodarczyk, Qiuying Chen, Nabeel Attarwala, Madhu Venkatesalu, Robert M. Cabrera, Steven S. Gross, Richard H. Finnell
Summary: In conclusion, the adverse effects of VPA on pregnancy may be related to embryonic hypotaurine levels, and supplementation of hypotaurine may reduce VPA-induced NTDs. In the sensitive strain, administration of hypotaurine significantly reduced the occurrence of NTDs, while L-carnitine and coenzyme A reduced resorption rates but did not significantly affect NTD risk.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Eirini Maniou, Michael F. Staddon, Abigail R. Marshall, Nicholas D. E. Greene, Andrew J. Copp, Shiladitya Banerjee, Gabriel L. Galea
Summary: Gap closure in mammalian embryos during embryonic hindbrain neuropore (HNP) closure follows specific mechanisms;
Asymmetric closure mechanisms involving pursestring contraction and directional cell motion accelerate the closure process;
Coordination of cellular and tissue-level mechanics is crucial for mammalian embryos to achieve this critical gap closure event.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Daisuke Sakai, Yuki Murakami, Daichi Shigeta, Mitsuhiro Tomosugi, Hiromi Sakata-Haga, Toshihisa Hatta, Hiroki Shoji
Summary: Physiological hypoxia is critical for placental mammalian development, but the mechanisms by which it regulates embryonic development are unclear. Our study found that the expression of glycolytic genes in neuroepithelial cells of E8.25 mouse embryos partially depends on hypoxia. Inhibiting glycolysis during the early phase of neural tube closure resulted in a defect, while inhibiting the electron transport chain had no effect. Additionally, inhibiting glycolysis affected cell proliferation, but not differentiation and survival, through the repression of myosin light chain 2 phosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Sidra Shafique, Louise M. Winn
Summary: This study demonstrated that in utero exposure to a teratogenic dose of VPA significantly downregulated mRNA levels of p65, Pim-1, and p105/p50 in CD-1 mouse embryos. Additionally, p65 protein expression was significantly upregulated in non-exencephalic embryos while p50 protein levels were significantly downregulated in both non-exencephalic and exencephalic groups at GD13. Furthermore, there were no changes in p65 and p50 protein levels in the nuclear extracts of VPA-exposed GD13 embryo heads.
NEUROTOXICOLOGY AND TERATOLOGY
(2021)
Article
Developmental Biology
Binbin Li, Liza Brusman, Jacob Dahlka, Lee A. Niswander
Summary: This study highlights the importance of mesoderm migration for spinal neural tube closure and implicates TMEM132A in regulating integrins and cell migration. Disruption of this process may lead to conditions like spina bifida.
Article
Cell Biology
Sarah Escuin, Saba Rose Raza-Knight, Dawn Savery, Carles Gaston-Massuet, Gabriel L. Galea, Nicholas D. E. Greene, Andrew J. Copp
Summary: Understanding the molecular mechanisms behind birth defects is crucial for preventing them. In mouse embryos with the Zic2Ku/Ku mutation, severe spina bifida occurs due to the absence of dorsolateral hinge points in the neuroepithelium. Overactivation of bone morphogenetic protein (BMP) and RhoA signaling is observed, leading to abnormal neural tube closure. The use of specific inhibitors reveals the involvement of both BMP-dependent DLHP formation and RhoA-dependent actomyosin accumulation in the pathogenesis of spina bifida. This study provides insights into the multifactorial origin of spina bifida in humans.
DISEASE MODELS & MECHANISMS
(2023)
Article
Cell Biology
Neophytos Christodoulou, Paris A. Skourides
Summary: Neural tube closure is a crucial process in vertebrate embryogenesis, and defects in this process can lead to common birth defects. This study investigates the mechanical communication between the neural plate and the somitic mesoderm and its impact on tissue morphogenesis using Xenopus laevis embryos.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Shih-Yin Ho, Li Lin, I-Chun Chen, Che-Wen Tsai, Fang-Chia Chang, Horng-Huei Liou
Summary: The study evaluated the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome, showing significant therapeutic potential in reducing spontaneous recurrent seizures and improving hyperthermia-induced seizures. PER also demonstrated a synergistic effect in combination with stiripentol or valproic acid for attenuating heat-induced seizures, highlighting its potential as a treatment option for Dravet syndrome.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Toxicology
Katharina Brotzmann, Andre Wolterbeek, Dinant Kroese, Thomas Braunbeck
Summary: The zebrafish embryo model shows potential as an alternative for teratogenicity testing in mammals, with a particular focus on neurodevelopmental endpoints. By analyzing specific neurodevelopmental endpoints in zebrafish embryos, the predictive power of the model for mammalian teratogenicity can be significantly improved.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zihao Deng, Marina R. Carpinelli, Tariq Butt, Graham W. Magor, Andrew C. Perkins, Stephen M. Jane
Summary: This study investigates the interaction between retinoic acid (RA) signaling and Grhl3-induced neural tube formation. The findings show that inhibition of RA signaling induces exencephaly and more severe spina bifida in mice lacking the Grhl3 gene. However, the timing of RA signaling inhibition does not affect the outcomes. These findings provide new insights into the understanding of neural tube defects (NTDs).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Anatomy & Morphology
Beatriz Fernandez-Santos, Jose Manuel Caro-Vega, Noelia Sola-Idigora, Cecilia Lazarini-Suarez, Laura Manas-Garcia, Patricia Duarte, Alejandro Fuerte-Hortigon, Patricia Ybot-Gonzalez
Summary: Neural tube closure is a complex developmental process involving the fusion of neural folds generated by the neural plate. Research indicates that similar cellular and molecular machinery is utilized in both the fusion of spinal neural folds and the repair of epithelial injury in embryos. Hyaluronic acid and platelet-derived growth factor signaling play crucial roles in the final fusion step during closure of caudal neural tissue.
DEVELOPMENTAL DYNAMICS
(2021)
Article
Developmental Biology
JiSoo Park, Hao-An Hsiung, Irina Khven, Gioele La Manno, Matthias P. Lutolf
Summary: A self-organizing 3D neural tube organoid model derived from single mouse embryonic stem cells was developed, exhibiting in vivo-like tissue architecture, cell type composition, and anterior-posterior patterning. The maturation of the neural tube organoids revealed the emergence of multipotent neural crest cells and mature neurons. Single-cell transcriptome analyses provided insights into the transcriptional events during neural crest cell emergence and neural differentiation.
Article
Cell Biology
Kwantae Kim, Jameson Orvis, Alberto Stolfi
Summary: Pax3/7 factors play crucial roles in the development of the nervous system in vertebrates and are also involved in similar functions in the model tunicate Ciona. The study reveals that Pax3/7 is expressed in the neural plate borders and central nervous system after neural tube closure, playing a conserved role in neural tube closure and neuron specification. These results suggest that the key functions of Pax3/7 in neural tube development are evolutionarily ancient, dating back to the common ancestor of vertebrates and tunicates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Environmental Sciences
Korawin Triyasakorn, Ubah Dominic Babah Ubah, Brandon Roan, Minsyusheen Conlin, Ken Aho, Prabha S. Awale
Summary: This study found that prenatal exposure to VPA significantly reduces the number of microglia during early postnatal brain development, which may be related to impaired connectivity in ASD.
Article
Reproductive Biology
Harm J. Heusinkveld, Yvonne C. M. Staal, Nancy C. Baker, George Daston, Thomas B. Knudsen, Aldert Piersma
Summary: In recent years, there has been a significant advancement in the development and implementation of animal-free approaches to chemical and pharmaceutical hazard and risk assessment, focusing on human biology and physiology. Research has shown that neural tube closure is a crucial step in early human development and is highly sensitive to chemical disturbances in signaling pathways. By mapping out the molecular regulation of neural tube closure, researchers aim to understand the genetic signals and responses underlying critical cellular processes, with the ultimate goal of constructing mathematical models and computer simulations for predicting toxicology.
REPRODUCTIVE TOXICOLOGY
(2021)
Article
Developmental Biology
Alexandra J. Palmer, Dawn Savery, Valentina Massa, Andrew J. Copp, Nicholas D. E. Greene
Summary: Mouse models are utilized to study genetic interactions leading to neural tube defects. This study investigated the potential interactions between Pax3 mutation and canonical Wnt signaling using conditional genetic models. The findings suggest that β-catenin function modulates the frequency of PAX3-related NTDs in mice, affecting both cranial and spinal neural tube closure differently.
Article
Multidisciplinary Sciences
Muzlifah Haniffa, Deanne Taylor, Sten Linnarsson, Bruce J. Aronow, Gary D. Bader, Roger A. Barker, Pablo G. Camara, J. Gray Camp, Alain Chedotal, Andrew Copp, Heather C. Etchevers, Paolo Giacobini, Berthold Gottgens, Guoji Guo, Ania Hupalowska, Kylie R. James, Emily Kirby, Arnold Kriegstein, Joakim Lundeberg, John C. Marioni, Kerstin B. Meyer, Kathy K. Niakan, Mats Nilsson, Bayanne Olabi, Dana Pe'er, Aviv Regev, Jennifer Rood, Orit Rozenblatt-Rosen, Rahul Satija, Sarah A. Teichmann, Barbara Treutlein, Roser Vento-Tormo, Simone Webb
Summary: The Human Developmental Cell Atlas initiative aims to create a comprehensive reference map of cells during development to understand the basis of human development, congenital and childhood disorders, as well as aging, cancer, and regenerative medicine. The initiative integrates scientists’ data on human development and uses state-of-the-art technologies to create a reference atlas across gestation.
Correction
Multidisciplinary Sciences
Gabriel L. Galea, Eirini Maniou, Timothy J. Edwards, Abigail R. Marshall, Ioakeim Ampartzidis, Nicholas D. E. Greene, Andrew J. Copp
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Oleksandr Nychyk, Gabriel L. Galea, Matteo Mole, Dawn Savery, Nicholas D. E. Greene, Philip Stanier, Andrew J. Copp
Summary: The study suggests that reduced sulfation of glycosaminoglycans interacting with heterozygosity for the Vangl2 gene may lead to craniorachischisis in mouse embryos, rather than defective neuroepithelial cell movements. Exogenous sulphate can rescue this defect.
DISEASE MODELS & MECHANISMS
(2022)
Letter
Developmental Biology
Andrew J. Copp, Nicholas D. E. Greene, Jennifer Jao, Rebecca Zash, Haneesha Mohan, Valeriya Dontsova, Lena Serghides
BIRTH DEFECTS RESEARCH
(2022)
Article
Genetics & Heredity
Siti Waheeda Mohd-Zin, Amelia Cheng Wei Tan, Wahib M. Atroosh, Meow-Keong Thong, Abu Bakar Azizi, Nicholas D. E. Greene, Noraishah Mydin Abdul-Aziz
Summary: This study analyzed Ephs-ephrins gene variants in Malaysian individuals with spina bifida and their family members, and found that some of them carried mutations in these genes. The variants were rare based on comparison with public databases.
Article
Developmental Biology
Yosuf Gheasuddin, Gabriel L. Galea
Summary: This study found that CBD acts as a neuroteratogen, increasing the risk of spina bifida and exencephaly in mouse embryo culture, without causing overt toxicity. Further large-scale testing is needed to understand the effects of CBD on neural tube closure, especially in at-risk groups.
BIRTH DEFECTS RESEARCH
(2022)
Article
Genetics & Heredity
Sophie Jamet, Seungshin Ha, Tzu-Hua Ho, Scott Houghtaling, Andrew Timms, Kai Yu, Alison Paquette, Ali Murat Maga, Nicholas D. E. Greene, David R. Beier
Summary: By performing ENU mutagenesis in mice and screening for mutations affecting embryonic development, we discovered a mutation in the Carm1 gene that is implicated in heart development defects. Our study found that Carm1 mutant mice exhibit various cardiac defects, including cardiac rupture, hemorrhaging, and different types of heart defects. Transcriptome analysis revealed the dysregulation of several genes involved in cardiac morphogenesis and muscle development and function.
G3-GENES GENOMES GENETICS
(2022)
Article
Nutrition & Dietetics
Eleanor Weston, Faith Pangilinan, Simon Eaton, Michael Orford, Kit-Yi Leung, Andrew J. Copp, James L. Mills, Anne M. Molloy, Lawrence C. Brody, Nicholas D. E. Greene
Summary: This study investigated the potential genetic regulation of plasma myo-inositol (MI) levels and found that the SLC5A11 gene may have a regulatory role in the plasma MI levels of young adults.
JOURNAL OF NUTRITION
(2022)
Article
Biology
Xiaoyu Che, Jufen Liu, Gabriel L. Galea, Yali Zhang, Nicholas D. E. Greene, Le Zhang, Lei Jin, Linlin Wang, Aiguo Ren, Zhiwen Li
Summary: Neural tube defects are severe congenital malformations, and folic acid supplementation can reduce their prevalence in northern China. The presence of comorbid malformations suggests a shared etiology.
Article
Cell Biology
Sarah Escuin, Saba Rose Raza-Knight, Dawn Savery, Carles Gaston-Massuet, Gabriel L. Galea, Nicholas D. E. Greene, Andrew J. Copp
Summary: Understanding the molecular mechanisms behind birth defects is crucial for preventing them. In mouse embryos with the Zic2Ku/Ku mutation, severe spina bifida occurs due to the absence of dorsolateral hinge points in the neuroepithelium. Overactivation of bone morphogenetic protein (BMP) and RhoA signaling is observed, leading to abnormal neural tube closure. The use of specific inhibitors reveals the involvement of both BMP-dependent DLHP formation and RhoA-dependent actomyosin accumulation in the pathogenesis of spina bifida. This study provides insights into the multifactorial origin of spina bifida in humans.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Zoe Crane-Smith, Sandra C. P. De Castro, Evanthia Nikolopoulou, Paul Wolujewicz, Damian Smedley, Yunping Lei, Emma Mather, Chloe Santos, Mark Hopkinson, Andrew A. Pitsillides, M. Elisabeth Genomics England Res Consortium, Richard H. Finnell, M. Elisabeth Ross, Andrew J. Copp, Nicholas D. E. Greene
Summary: Orofacial clefts and neural tube defects are common congenital anomalies, and the genetic basis for these conditions is still not fully understood. Excess expression of the Grhl2 gene causes various defects in mice, including orofacial clefts and abnormalities in the craniofacial region. Further analysis revealed a retrotransposon insertion in the regulatory region of Grhl2, which may contribute to craniofacial anomalies and neural tube defects in humans.
HUMAN MOLECULAR GENETICS
(2023)