Arterial dysgenesis and limb defects : Clinical and experimental examples

Acknowledgements This article is dedicated to Dr David S. Packard Jr. With thanks to Dr John DeSesso, Dr Lewis B. Holmes, Dr Mark Levinsohn, Dr David S. Packard Jr, Prof Lewis Wolpert for discussions on vascular disruption, particularly arterial dysgenesis and limb defects. We apologise to the many authors whose work we were unable to cite due to space limitations. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin

Quantitative assessment of intrinsic noise for visually guided behaviour in zebrafish

Supported by Royal Society of London (University Research Fellowship), Medical Research Council (New Investigator Research Grant) and CNRS.Peer reviewedPostprin

Thalidomide embryopathy : an enigmatic challenge

Thanks go to Dr. Chris Mahony, Prof. Martin Collinson, Shaunna-Leigh Beedie and Alexandra Diamond for critical comments on the paper. Thanks also go to Prof. Lynda Erskine, Dr. W. D. Figg, Dr. Lavinia Schuler-Faccini, Dr. Robert L. Smith, Prof. Nigel Brown, Prof. Ruth Ross, Prof. Cheryll Tickle and Prof. Lewis Wolpert for fantastic discussions on thalidomide. This work is dedicated to C. G. V. and C. W. M. V.Peer reviewedPublisher PD

"The legacy of thalidomide" - A multidisciplinary meeting held at the University of York, United Kingdom, on September 30, 2016 : A multidisciplinary meeting held at the University of York, UK on September 30, 2016

BACKGROUND: Between 1957 and 1962 thalidomide was used as a nonaddictive, nonbarbiturate sedative that also was successful in relieving the symptoms of morning sickness in early pregnancy. Infamously, thousands of babies were subsequently born with severe birth defects. The drug is used again, today, to successfully treat leprosy, and tragically, there is a new generation of thalidomide damaged children in Brazil. While the outward damage in babies has been documented, the effects of the damage upon the survivors as they grow up, the lifestyle changes and adaptations required to be made, as well as studies into ageing in survivors, has received little attention and remains understudied. METHODS: A unique multidisciplinary meeting was organized at the University of York bringing together thalidomide survivors, clinicians, scientists, historians, and social scientists to discuss the past, the current and the future implications of thalidomide. RESULTS: There is still much to learn from thalidomide, from its complex history and ongoing impact on peoples' lives today, to understanding its mechanism/s to aid future drug safety, to help identify new drugs retaining clinical benefit without the risk of causing embryopathy. CONCLUSION: For thalidomide survivors, the original impairments caused by the drug are compounded by the consequences of a lifetime of living with a rare disability, and early onset age-related health problems. This has profound implications for their quality of life and need for health and social care services. It is vital that these issues are addressed in research, and in clinical practice if thalidomide survivors are to "age well". Birth Defects Research 109:296-299, 2017. © 2017 Wiley Periodicals, Inc

The teratogenic effects of thalidomide on limbs

Acknowledgements Thanks to members of the Thalidomide Society for helpful discussions on thalidomide-induced limb damage. Funding The author disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research in the lab has previously been sponsored by Wellcome Trust, Royal Society and University of Aberdeen.Peer reviewedPostprin

Smad7 Misexpression during Embryonic Angiogenesis Causes Vascular Dilation and Malformations Independently of Vascular Smooth Muscle Cell Function

AbstractNumerous in vitro and in vivo studies implicate transforming growth factor-β (TGFβ) superfamily signaling in vascular development and maintenance. Mice and humans with mutations in TGFβ superfamily signaling pathway genes exhibit a range of vascular defects that include dilated, fragile and hemorrhagic vessels, defective angiogenic remodeling, severe vascular malformations including arterio-venous malformations, and disrupted vascular smooth muscle cell recruitment and maintenance. Despite a wealth of data, the functions of TGFβ superfamily signals during angiogenesis are poorly defined, since early embryonic lethality and difficulty distinguishing between primary and secondary defects frequently confound phenotypic interpretation. To perturb TGFβ superfamily signaling during angiogenesis, we have misexpressed Smad7, an intracellular antagonist of TGFβ superfamily signaling, in the developing chick limb and head. We find that the great vessels are strikingly dilated and frequently develop intra and intervascular shunts. Neither noggin nor dominant negative BMP receptor misexpression causes similar vascular phenotypes. However, simultaneous misexpression of constitutively active BMP receptors with Smad7 suppresses the Smad7-induced phenotype, suggesting that a BMP-like intracellular pathway is the target of Smad7 action. Despite the gross morphological defects, further analyses find no evidence of hemorrhage and vessel structure is normal. Furthermore, enlarged vessels and vascular malformations form in either the presence or absence of vascular smooth muscle, and vascular smooth muscle cell recruitment is unperturbed. Our data define the TGFβ superfamily pathway as an integral regulator of vessel caliber that is also essential for appropriate vessel connectivity. They demonstrate that dilation need not result in vessel rupture or hemorrhage, and dissociate vessel maintenance from the presence of a vascular smooth muscle cell coat. Furthermore they uncouple vascular smooth muscle cell recruitment and differentiation from TGFβ superfamily signaling

CPS49-induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos

The authors thank Elizabeth Kilby and Susan Reijntes for preliminary studies. CM was funded by a University of Aberdeen PhD studentship; AJR (née Diamond) was funded through a BBSRC EastBio DTP PhD Award; S-L B was funded by a Wellcome Trust/NIH PhD Studentship; SM was funded by a Siddall PhD Scholarship Award; LRF was funded by the Science Without Borders PhD Scheme.Peer reviewedPostprin

Thalidomide: History, withdrawal, renaissance and safety concerns

Peer reviewedPostprin

Thalidomide and birth defects

Apologies to the many papers we were unable to cite, due to space constraints. We thank Lynda Erskine, Shaunna Beedie and Chris Mahony for helpful discussions. Lucas Rosa Fraga is funded by a PhD scholarship from the Science without Borders program - CNPq Brazil - INAGEMP/ Grant CNPq 573993/2008-4. Alex J. Diamond is funded by a BBSRC DTP PhD Scholarship.Peer reviewedPostprin

Vascular anomalies of the upper limb

Acknowledgements: The authors would like to thank Selina Ackermann for her great help with the editing of this article. Funding: The authors received no financial support for the research, authorship, and/or publication of this article.Peer reviewedPostprin