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Article ; Online: Jurisdictional context and the (over)use of pretrial detention.

Ranson, J W Andrew / Arnio, Ashley N / Copp, Jennifer E

Social science research

2023 Volume 112, Page(s) 102872

Language	English
Publishing date	2023-03-16
Publishing country	United States
Document type	Journal Article
ISSN	1096-0317
ISSN (online)	1096-0317
DOI	10.1016/j.ssresearch.2023.102872
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Article ; Online: Live-Imaging Analysis of Epithelial Zippering During Mouse Neural Tube Closure.

Molè, Matteo A / Galea, Gabriel L / Copp, Andrew J

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2608, Page(s) 147–162

Abstract: Zippering is a phenomenon of tissue morphogenesis whereby fusion between opposing epithelia progresses unidirectionally over significant distances, similar to the travel of a zip fastener, to ultimately ensure closure of an opening. A comparable process ... ...

Abstract	Zippering is a phenomenon of tissue morphogenesis whereby fusion between opposing epithelia progresses unidirectionally over significant distances, similar to the travel of a zip fastener, to ultimately ensure closure of an opening. A comparable process can be observed during Drosophila dorsal closure and mammalian wound healing, while zippering is employed by numerous organs such as the optic fissure, palatal shelves, tracheoesophageal foregut, and presumptive genitalia to mediate tissue sealing during normal embryonic development. Particularly striking is zippering propagation during neural tube morphogenesis, where the fusion point travels extensively along the embryonic axis to ensure closure of the neural tube. Advances in time-lapse microscopy and culture conditions have opened the opportunity for successful imaging of whole-mouse embryo development over time, providing insights into the precise cellular behavior underlying zippering propagation. Studies in mouse and the ascidian Ciona have revealed the fine-tuned cell shape changes and junction remodeling which occur at the site of zippering during neural tube morphogenesis. Here, we describe a step-by-step method for imaging at single-cell resolution the process of zippering and tissue remodeling which occurs during closure of the spinal neural tube in mouse. We also provide instructions and suggestions for quantitative morphometric analysis of cell behavior during zippering progression. This procedure can be further combined with genetic mutant models (e.g., knockouts), offering the possibility of studying the dynamics of tissue fusion and zippering propagation, which underlie a wide range of open neural tube defects.
MeSH term(s)	Animals ; Mice ; Neural Tube ; Neurulation ; Morphogenesis ; Embryonic Development ; Epithelium ; Drosophila ; Mammals
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2887-4_10
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Article: Morphological phenotyping after mouse whole embryo culture.

Copp, Andrew J / Clark, Maryam / Greene, Nicholas D E

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1223849

Abstract: Morphological phenotyping of the mouse embryo is described at neurulation stages, primarily as a guide to evaluating the outcome of whole embryo cultures between embryonic days 8.5 and 9.5. During this period, neural tube closure is initiated and ... ...

Abstract	Morphological phenotyping of the mouse embryo is described at neurulation stages, primarily as a guide to evaluating the outcome of whole embryo cultures between embryonic days 8.5 and 9.5. During this period, neural tube closure is initiated and progresses to completion in the cranial region. Spinal closure is still underway at the end of the culture period. The focus of this article is particularly on phenotyping that can be performed at the bench, using a stereomicroscope. This involves assessment of embryonic health, through observation and scoring of yolk sac blood circulation, measurement of developmental stage by somite counting, and determination of crown-rump length as a measure of growth. Axial rotation ("turning") can also be assessed using a simple scoring system. Neural tube closure assessment includes: 1) determining whether closure has been initiated at the Closure 1 site; 2) evaluating the complex steps of cranial neurulation including initiation at Closure sites 2 and 3, and completion of closure at the anterior and hindbrain neuropores; 3) assessment of spinal closure by measurement of posterior neuropore length. Interpretation of defects in neural tube closure requires an appreciation of, first, the stages that particular events are expected to be completed and, second, the correspondence between embryonic landmarks, for example, somite position, and the resulting adult axial levels. Detailed embryonic phenotyping, as described in this article, when combined with the versatile method of whole embryo culture, can form the basis for a wide range of experimental studies in early mouse neural development.
Language	English
Publishing date	2023-08-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1223849
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Article ; Online: A topographical analysis of encephalocele locations: generation of a standardised atlas and cluster analysis.

Vakharia, Vejay Niranjan / Toescu, Sebastien / Copp, Andrew J / Thompson, Dominic N P

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

2023 Volume 39, Issue 7, Page(s) 1911–1920

Abstract: Objective: Encephaloceles are considered to result from defects in the developing skull through which meninges, and potentially brain tissue, herniate. The pathological mechanism underlying this process is incompletely understood. We aimed to describe ... ...

Abstract	Objective: Encephaloceles are considered to result from defects in the developing skull through which meninges, and potentially brain tissue, herniate. The pathological mechanism underlying this process is incompletely understood. We aimed to describe the location of encephaloceles through the generation of a group atlas to determine whether they occur at random sites or clusters within distinct anatomical regions. Methods: Patients diagnosed with cranial encephaloceles or meningoceles were identified from a prospectively maintained database between 1984 and 2021. Images were transformed to atlas space using non-linear registration. The bone defect, encephalocele and herniated brain contents were manually segmented allowing for a 3-dimensional heat map of encephalocele locations to be generated. The centroids of the bone defects were clustered utilising a K-mean clustering machine learning algorithm in which the elbow method was used to identify the optimal number of clusters. Results: Of the 124 patients identified, 55 had volumetric imaging in the form of MRI (48/55) or CT (7/55) that could be used for atlas generation. Median encephalocele volume was 14,704 (IQR 3655-86,746) mm Conclusion: This analysis revealed three predominant clusters for the location of encephaloceles, with the parieto-occipital junction being the most common. The stereotypic location of encephaloceles into anatomically distinct clusters and the coexistence of distinct venous malformations at certain sites suggests that their location is not random and raises the possibility of distinct pathogenic mechanisms unique to each of these regions.
MeSH term(s)	Humans ; Encephalocele/pathology ; Skull/pathology ; Meningocele/surgery ; Brain/pathology ; Cluster Analysis
Language	English
Publishing date	2023-03-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	605988-0
ISSN	1433-0350 ; 0302-2803 ; 0256-7040
ISSN (online)	1433-0350
ISSN	0302-2803 ; 0256-7040
DOI	10.1007/s00381-023-05883-7
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Article ; Online: The surface ectoderm exhibits spatially heterogenous tension that correlates with YAP localisation during spinal neural tube closure in mouse embryos.

Marshall, Abigail R / Galea, Gabriel L / Copp, Andrew J / Greene, Nicholas D E

Cells & development

2023 Volume 174, Page(s) 203840

Abstract: The single cell layer of surface ectoderm (SE) which overlies the closing neural tube (NT) plays a crucial biomechanical role during mammalian NT closure (NTC), challenging previous assumptions that it is only passive to the force-generating ... ...

Abstract	The single cell layer of surface ectoderm (SE) which overlies the closing neural tube (NT) plays a crucial biomechanical role during mammalian NT closure (NTC), challenging previous assumptions that it is only passive to the force-generating neuroepithelium (NE). Failure of NTC leads to congenital malformations known as NT defects (NTDs), including spina bifida (SB) and anencephaly in the spine and brain respectively. In several mouse NTD models, SB is caused by misexpression of SE-specific genes and is associated with disrupted SE mechanics, including loss of rostrocaudal cell elongation believed to be important for successful closure. In this study, we asked how SE mechanics affect NT morphology, and whether the characteristic rostrocaudal cell elongation at the progressing closure site is a response to tension anisotropy in the SE. We show that blocking SE-specific E-cadherin in ex utero mouse embryo culture influences NT morphology, as well as the F-actin cable. Cell border ablation shows that cell shape is not due to tension anisotropy, but that there are regional differences in SE tension. We also find that YAP nuclear translocation reflects regional tension heterogeneity, and that its expression is sensitive to pharmacological reduction of tension. In conclusion, our results confirm that the SE is a biomechanically important tissue for spinal NT morphogenesis and suggest a possible role of spatial regulation of cellular tension which could regulate downstream gene expression via mechanically-sensitive YAP activity.
MeSH term(s)	Mice ; Animals ; Ectoderm ; Neural Tube ; Neural Tube Defects/genetics ; Spinal Dysraphism/genetics ; Spinal Dysraphism/complications ; Spine ; Disease Models, Animal ; Mammals
Language	English
Publishing date	2023-04-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2667-2901
ISSN (online)	2667-2901
DOI	10.1016/j.cdev.2023.203840
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Article ; Online: Metabolic implications and safety of dolutegravir use in pregnancy.

Dontsova, Valeriya / Mohan, Haneesha / Blanco, Camille / Jao, Jennifer / Greene, Nicholas D E / Copp, Andrew J / Zash, Rebecca / Serghides, Lena

The lancet. HIV

2023 Volume 10, Issue 9, Page(s) e606–e616

Abstract: Dolutegravir is recommended for all people living with HIV because of its efficacy, high barrier to resistance, favourable safety and tolerability profile, and affordability. Dolutegravir has the highest rates of viral suppression in pregnancy, therefore ...

Abstract	Dolutegravir is recommended for all people living with HIV because of its efficacy, high barrier to resistance, favourable safety and tolerability profile, and affordability. Dolutegravir has the highest rates of viral suppression in pregnancy, therefore preventing perinatal HIV transmission. In view of these benefits, particularly for pregnant women, an important question is if dolutegravir is safe in pregnancy. Dolutegravir has been associated with metabolic complications, including weight gain and rare events of hyperglycaemia, that could affect maternal, fetal, and postnatal health. We review the current clinically and experimentally based literature on the implications of dolutegravir use for pregnant women and for developing embryos and fetuses. Possible effects on folate status, energy metabolism, adipogenesis, and oxidative stress are considered. In many instances, insufficient data are available, pointing to the need for additional research in this important area of HIV treatment.
MeSH term(s)	Pregnancy ; Humans ; Female ; HIV Infections/drug therapy ; Oxazines ; Heterocyclic Compounds, 3-Ring/adverse effects ; Piperazines
Chemical Substances	dolutegravir (DKO1W9H7M1) ; Oxazines ; Heterocyclic Compounds, 3-Ring ; Piperazines
Language	English
Publishing date	2023-08-04
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ISSN	2352-3018
ISSN (online)	2352-3018
DOI	10.1016/S2352-3018(23)00141-8
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Article ; Online: Dual mechanism underlying failure of neural tube closure in the Zic2 mutant mouse.

Escuin, Sarah / Rose Raza-Knight, Saba / Savery, Dawn / Gaston-Massuet, Carles / Galea, Gabriel L / Greene, Nicholas D E / Copp, Andrew J

Disease models & mechanisms

2023 Volume 16, Issue 3

Abstract: Understanding the molecular mechanisms that lead to birth defects is an important step towards improved primary prevention. Mouse embryos homozygous for the Kumba (Ku) mutant allele of Zic2 develop severe spina bifida with complete lack of dorsolateral ... ...

Abstract	Understanding the molecular mechanisms that lead to birth defects is an important step towards improved primary prevention. Mouse embryos homozygous for the Kumba (Ku) mutant allele of Zic2 develop severe spina bifida with complete lack of dorsolateral hinge points (DLHPs) in the neuroepithelium. Bone morphogenetic protein (BMP) signalling is overactivated in Zic2Ku/Ku embryos, and the BMP inhibitor dorsomorphin partially rescues neural tube closure in cultured embryos. RhoA signalling is also overactivated, with accumulation of actomyosin in the Zic2Ku/Ku neuroepithelium, and the myosin inhibitor Blebbistatin partially normalises neural tube closure. However, dorsomorphin and Blebbistatin differ in their effects at tissue and cellular levels: DLHP formation is rescued by dorsomorphin but not Blebbistatin, whereas abnormal accumulation of actomyosin is rescued by Blebbistatin but not dorsomorphin. These findings suggest a dual mechanism of spina bifida origin in Zic2Ku/Ku embryos: faulty BMP-dependent formation of DLHPs and RhoA-dependent F-actin accumulation in the neuroepithelium. Hence, we identify a multi-pathway origin of spina bifida in a mammalian system that may provide a developmental basis for understanding the corresponding multifactorial human defects.
MeSH term(s)	Mice ; Animals ; Humans ; Neural Tube/metabolism ; Actomyosin/metabolism ; Spinal Dysraphism ; Neural Tube Defects/genetics ; Neurulation ; Mammals/metabolism ; Nuclear Proteins/metabolism ; Transcription Factors/metabolism
Chemical Substances	Actomyosin (9013-26-7) ; ZIC2 protein, human ; Nuclear Proteins ; Transcription Factors
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.049858
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Book: Postimplantation mammalian embryos

Copp, Andrew J.

a practical approach

(Practical approach series ; [69])

1990

Author's details	ed. by A. J. Copp
Series title	Practical approach series ; [69] The practical approach series
Collection	The practical approach series
Keywords	Embryo
Size	XXI, 357 S. : Ill., graph. Darst.
Publisher	IRL Pr
Publishing place	Oxford u.a.
Publishing country	Great Britain
Document type	Book
HBZ-ID	HT003742226
ISBN	0-19-963088-7 ; 978-0-19-963088-2
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
1991 A 1442	order for loan	Magazin

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Article ; Online: Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects.

Peake, Jordana N / Knowles, Rachel L / Shawe, Jill / Rankin, Judith / Copp, Andrew J

Birth defects research

2021 Volume 113, Issue 12, Page(s) 968–980

Abstract: Background: Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD-affected pregnancies, classified by maternal ... ...

Abstract	Background: Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD-affected pregnancies, classified by maternal ethnicity, and to explore why variations in prevalence might exist. Methods: A cross-sectional study was performed with data from regional congenital anomaly registers in England and Wales, for NTD-affected pregnancies between 2006 and 2011. Using binomial regression models, we examined NTD-affected pregnancy prevalence estimates and rate ratios (PRRs), by maternal ethnicity. Results: The prevalence of NTDs was 12.14 per 10,000 births, with no differences between study years. Anencephaly, encephalocele and spina bifida occurred at 4.98, 1.37 and 5.80 per 10,000 births respectively. Mothers of Indian ethnicity were 1.84 times more likely (95% CI: 1.24, 2.73) and Bangladeshi mothers 2.86 times more likely (95% CI: 1.48, 5.53) than White mothers to have an NTD-affected pregnancy, after adjusting for maternal deprivation and maternal age. The excess prevalence in Indian mothers was specifically for anencephaly (PRR 2.57; 95% CI: 1.52, 4.34), and in Bangladeshi mothers the trend was for increased spina bifida (PRR 3.86; 95% CI: 0.72, 8.69). Anencephaly in Indian mothers was especially associated with other congenital anomalies (non-isolated NTDs). Conclusions: Different British ethnic groups vary in NTD prevalence. The excess prevalence of anencephaly as a non-isolated NTD in pregnancies of Indian mothers could indicate involvement of genetic or other unmeasured behavioral factors. Future work is needed to seek etiological explanations for the ethnicity differences and to develop improved methods for primary prevention.
MeSH term(s)	Anencephaly/epidemiology ; Cross-Sectional Studies ; Ethnicity ; Female ; Humans ; Neural Tube Defects/epidemiology ; Pregnancy ; Prevalence
Language	English
Publishing date	2021-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2104792-3
ISSN	2472-1727
ISSN (online)	2472-1727
DOI	10.1002/bdr2.1893
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Zs.A 749: Show issues

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Article ; Online: Genetic interaction of Pax3 mutation and canonical Wnt signaling modulates neural tube defects and neural crest abnormalities.

Palmer, Alexandra J / Savery, Dawn / Massa, Valentina / Copp, Andrew J / Greene, Nicholas D E

Genesis (New York, N.Y. : 2000)

2021 Volume 59, Issue 11, Page(s) e23445

Abstract: Mouse models provide opportunities to investigate genetic interactions that cause or modify the frequency of neural tube defects (NTDs). Mutation of the PAX3 transcription factor prevents neural tube closure, leading to cranial and spinal NTDs whose ... ...

Abstract	Mouse models provide opportunities to investigate genetic interactions that cause or modify the frequency of neural tube defects (NTDs). Mutation of the PAX3 transcription factor prevents neural tube closure, leading to cranial and spinal NTDs whose frequency is responsive to folate status. Canonical Wnt signalling is implicated both in regulation of Pax3 expression and as a target of PAX3. This study investigated potential interactions of Pax3 mutation and canonical Wnt signalling using conditional gain- and loss-of-function models of β-catenin. We found an additive effect of β-catenin gain of function and Pax3 loss of function on NTDs and neural crest defects. β-catenin gain of function in the Pax3 expression domain led to significantly increased frequency of cranial but not spinal NTDs in embryos that are heterozygous for Pax3 mutation, while both cranial and spinal neural tube closure were exacerbated in Pax3 homozygotes. Similarly, deficits of migrating neural crest cells were exacerbated by β-catenin gain of function, with almost complete ablation of spinal neural crest cells and derivatives in Pax3 homozygous mutants. Pax3 expression was not affected by β-catenin gain of function, while we confirmed that loss of function led to reduced Pax3 transcription. In contrast to gain of function, β-catenin knockout in the Pax3 expression domain lowered the frequency of cranial NTDs in Pax3 null embryos. However, loss of function of β-catenin and Pax3 resulted in spinal NTDs, suggesting differential regulation of cranial and spinal neural tube closure. In summary, β-catenin function modulates the frequency of PAX3-related NTDs in the mouse.
MeSH term(s)	Animals ; Heterozygote ; Mice ; Mice, Inbred C57BL ; Mutation ; Neural Crest/abnormalities ; Neural Crest/embryology ; Neural Crest/metabolism ; Neural Tube Defects/genetics ; PAX3 Transcription Factor/genetics ; PAX3 Transcription Factor/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	PAX3 Transcription Factor ; beta Catenin ; Pax3 protein, mouse (138016-91-8)
Language	English
Publishing date	2021-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2004544-X
ISSN	1526-968X ; 1526-954X
ISSN (online)	1526-968X
ISSN	1526-954X
DOI	10.1002/dvg.23445
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