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Stampeding Embryo Cells Print E-mail
SciMed - Biology
TS-Si News Service   
Wednesday, 02 March 2011 15:00
Embryonic Visceral EndodermOxford, UK. As an embryo grows towards its final adult form, the initial fertilized egg cell must divide many times over into cells that will become specialized and form the many different tissues and organs of the body.

This process of embryo development is a dynamic one, as the time-lapse video of microscope images illustrates below.

Cells don’t just sense their specific position in the growing embryo and develop into the appropriate (i.e., target) tissue. They move around and migrate to where they need to be for target formation.

Dr Shankar Srinivas and colleagues in the Department of Physiology, Anatomy and Genetics at the University of Oxford are working on the molecular signals that govern these cell migrations in the early embryo. Should this development be disrupted, the embryo may not be viable or it could lead to birth abnormalities. While the work focuses on mouse embryos, the molecular pathways identified will have equivalents in humans.



Tracks of VE cells in different regions of the embryo

Video courtesy of the Shankar Srinivas Lab, University of Oxford Time: 00:00:05.
The video at right is from an article in the journal PLoS Biology. It shows that an important set of cells (tagged with a green marker in the left-hand video) — which determine where the head of the embryo will be — move up through the growing embryo, nudging aside neighbouring cells to get where they need to be.

The same cells are colored green again, while another type of migrating cell is magenta. Static cells, colored blue, form a barrier to stop both sets migrating too far.

Technical Description

Time-lapse sequence of an embryo showing differences in behaviour between Epi-VE and ExE-VE cells. Images were taken every 15 min. The embryo is oriented with the anterior toward the viewer. AVE cells are marked by Hex-GFP expression (green) in the left-hand side panel.

In the panel to the right, the GFP channel has been removed and cells outlined to help follow them. AVE cells and their projections are in green, non-AVE Epi-VE cells are magenta, and ExE-VE cells are blue.

The basal projections of AVE cells can be seen “overlapping” with the magenta Epi-VE cells ahead of them. The last frame shows the tracks of the marked cells. Use the keyboard arrow keys to navigate frame by frame.

CitationNodal Dependent Differential Localisation of Dishevelled-2 Demarcates Regions of Differing Cell Behaviour in the Visceral Endoderm. Georgios Trichas, Bradley Joyce, Lucy A. Crompton, Vivienne Wilkins, Melanie Clements, Masazumi Tada, Tristan A. Rodriguez, Shankar Srinivas. PLoS Biology 9(2): e1001019. doi:10.1371/journal.pbio.1001019
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Abstract

The anterior visceral endoderm (AVE), a signalling centre within the simple epithelium of the visceral endoderm (VE), is required for anterior-posterior axis specification in the mouse embryo. AVE cells migrate directionally within the VE, thereby properly positioning the future anterior of the embryo and orientating the primary body axis. AVE cells consistently come to an abrupt stop at the border between the anterior epiblast and extra-embryonic ectoderm, which represents an end-point to their proximal migration. Little is known about the underlying basis for this barrier and how surrounding cells in the VE respond to or influence AVE migration. We use high-resolution 3D reconstructions of protein localisation patterns and time-lapse microscopy to show that AVE cells move by exchanging neighbours within an intact epithelium. Cell movement and mixing is restricted to the VE overlying the epiblast, characterised by the enrichment of Dishevelled-2 (Dvl2) to the lateral plasma membrane, a hallmark of Planar Cell Polarity (PCP) signalling. AVE cells halt upon reaching the adjoining region of VE overlying the extra-embryonic ectoderm, which displays reduced neighbour exchange and in which Dvl2 is excluded specifically from the plasma membrane. Though a single continuous sheet, these two regions of VE show distinct patterns of F-actin localisation, in cortical rings and an apical shroud, respectively. We genetically perturb PCP signalling and show that this disrupts the localisation pattern of Dvl2 and F-actin and the normal migration of AVE cells. In Nodal null embryos, membrane localisation of Dvl2 is reduced, while in mutants for the Nodal inhibitor Lefty1, Dvl2 is ectopically membrane localised, establishing a role for Nodal in modulating PCP signalling. These results show that the limits of AVE migration are determined by regional differences in cell behaviour and protein localisation within an otherwise apparently uniform VE. In addition to coordinating global cell movements across epithelia (such as during convergence extension), PCP signalling in interplay with TGFß signalling can demarcate regions of differing behaviour within epithelia, thereby modulating the movement of cells within them.

Author Summary

he orientation of the head-tail axis is determined during embryogenesis by the movements of a subset of cells called the AVE (anterior visceral endoderm). These cells migrate from their initial position within the simple epithelium of the visceral endoderm (VE) to a location from which they eventually induce anterior pattern in the adjacent epiblast. Little is understood about how AVE cells migrate within the VE, why they stop migrating where they do, and how surrounding cells in the VE respond to or influence AVE migration. In this study, we use time-lapse microscopy and high-resolution 3D reconstructions of protein localisation patterns to address these issues. Our results show that AVE cells move by exchanging neighbours within an intact epithelium. The limits of AVE migration are determined by regional differences in cell behaviour and protein localisation within an otherwise apparently uniform VE. Finally, we examine the role of planar cell polarity (PCP) signalling, which is responsible for coordinating morphogenetic events across different epithelia. We show that in addition to this traditional role in coordinating global cell movements, PCP signalling along with TGFß signalling can demarcate regions of differing behaviour within epithelia, thereby modulating the movement of cells within them.

Abbreviations: dpc, days post coitum; dvl2, dishevelled-2; epi-ve, ve overlying epiblast; exe, extraembryonic ectoderm; exe-ve, ve overlying exe; pcp, planar cell polarity; ve, visceral endoderm.

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Stampeding Embryo Cells
Wednesday, 02 March 2011

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Last Updated on Tuesday, 01 March 2011 20:53
 
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