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Cambridge, United Kingdom

England S.,Syracuse University | Batista M.F.,Development and Neuroscience | Mich J.K.,Stanford University | Chen J.K.,Stanford University | Lewis K.E.,Syracuse University
Development | Year: 2011

SUMMARY In mouse, Hedgehog (Hh) signalling is required for most ventral spinal neurons to form. Here, we analyse the spinal cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signalling. We find that most V3 domain cells and motoneurons are lost, whereas medial floorplate still develops normally and V2, V1 and V0v cells form in normal numbers. This phenotype resembles that of mice that lack both Hh signalling and Gli repressor activity. Ventral spinal cord progenitor domain transcription factors are not expressed at 24 hpf in zebrafish MZsmo mutants. However, pMN, p2 and p1 domain markers are expressed at early somitogenesis stages in these mutants. This suggests that Gli repressor activity does not extend into zebrafish ventral spinal cord at these stages, even in the absence of Hh signalling. Consistent with this, ectopic expression of Gli3R represses ventral progenitor domain expression at these early stages and knocking down Gli repressor activity rescues later expression. We investigated whether retinoic acid (RA) signalling specifies ventral spinal neurons in the absence of Hh signalling. The results suggest that RA is required for the correct number of many different spinal neurons to form. This is probably mediated, in part, by an effect on cell proliferation. However, V0v, V1 and V2 cells are still present, even in the absence of both Hh and RA signalling. We demonstrate that Gli1 has a Hh-independent role in specifying most of the remaining motoneurons and V3 domain cells in embryos that lack Hh signalling, but removal of Gli1 activity does not affect more dorsal neurons. © 2011. Published by The Company of Biologists Ltd. Source

Birschwilks M.,Federal office for Radiation Protection | Schofield P.N.,Development and Neuroscience | Grosche B.,Federal office for Radiation Protection
Health Physics | Year: 2012

The European Radiobiological Archive can be accessed at no cost at https://era.bfs.de. The necessary ID and password can be obtained from the curators at era@bfs.de. Copyright © 2012 Health Physics Society. Source

Burton G.J.,Development and Neuroscience
Reproductive BioMedicine Online | Year: 2012

The placenta is an essential but widely neglected organ. As the interface between the mother and her fetus, the placenta represents the platform for a healthy life. The majority of the major complications of pregnancy, including miscarriage, pre-eclampsia, intrauterine growth restriction and stillbirth, have their pathophysiological roots in poor placentation. In addition, there is now irrefutable evidence that low birthweight predisposes to a higher risk of cardiovascular and other disorders in later life. The Centre for Trophoblast Research was established in the University of Cambridge with the aim of generating new impetus and a fresh approach to address these problems. Placentation involves many different cell biological processes, some of which are unique to the trophoblast, as well as complex interactions with the maternal immune system. The Centre brings together academic clinicians and basic scientists working in diverse disciplines and provides a rich intellectual environment that facilitates novel collaborative links. The Centre also encourages new investigators into the field and fosters their careers through a number of initiatives, including support for studentships and fellowships, developing research resources, hosting an annual scientific meeting and running a training course in placental biology. Full details can be found at www.trophoblast.cam.ac.uk. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source

Gkoutos G.V.,University of Cambridge | Gkoutos G.V.,Aberystwyth University | Schofield P.N.,Development and Neuroscience | Hoehndorf R.,University of Cambridge
International Review of Neurobiology | Year: 2012

In recent years, considerable advances have been made toward our understanding of the genetic architecture of behavior and the physical, mental, and environmental influences that underpin behavioral processes. The provision of a method for recording behavior-related phenomena is necessary to enable integrative and comparative analyses of data and knowledge about behavior. The neurobehavior ontology facilitates the systematic representation of behavior and behavioral phenotypes, thereby improving the unification and integration behavioral data in neuroscience research. © 2012 Elsevier Inc. Source

Genetic 'signatures' of early-stage embryos confirm that our development begins to take shape as early as the second day after conception, when we are a mere four cells in size, according to new research led by the University of Cambridge and EMBL-EBI. Although they seem to be identical, the cells of the two day-old embryo are already beginning to display subtle differences. Once an egg has been fertilised by a sperm, it divides several times, becoming a large free-floating ball of stem cells. At first, these stem cells are 'totipotent', the state at which a stem cell can divide and grow and produce everything—every single cell of the whole body and the placenta, to attach the embryo to the mother's womb. The stem cells then change to a 'pluripotent' state, in which their development is restricted to generating the cells of the whole body, but not the placenta. However, the point during development at which cells begin to show a preference for becoming a specific cell type is unclear. Now, in a study published in the journal Cell, scientists at the University of Cambridge and the European Bioinformatics Institute (EMBL-EBI) suggests that as early as the four-cell embryo stage, the cells are indeed different. The researchers used the latest sequencing technologies to model embryo development in mice, looking at the activity of individual genes at a single cell level. They showed that some genes in each of the four cells behaved differently. The activity of one gene in particular, Sox21, differed the most between cells; this gene forms part of the 'pluripotency network'. The team found when this gene's activity was reduced, the activity of a master regulator that directs cells to develop into the placenta increased. "We know that life starts when a sperm fertilises an egg, but we're interested in when the important decisions that determine our future development occur," says Professor Magdalena Zernicka-Goetz from the Department of Physiology, Development and Neuroscience at the University of Cambridge. "We now know that even as early as the four-stage embryo - just two days after fertilisation - the embryo is being guided in a particular direction and its cells are no longer identical." Dr John Marioni of EMBL-EBI, the Wellcome Trust Sanger Institute and the Cancer Research UK Cambridge Institute, adds: "We can make use of powerful sequencing tools to deepen our understanding of the molecular mechanisms that drive development in individual cells. Because of these high-resolution techniques, we are now able to see the genetic and epigenetic signatures that indicate the direction in which early embryonic cells will tend to travel." More information: Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in Four-Cell Mouse Embryos. Cell; 24 March 2016. DOI: 10.1016/j.cell.2016.01.047

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