Researchers visualise mammalian embryo formation for the first time.


Mammalian embryos start out as a small group of identical cells. Then at an early stage, some of these cells take up an internal position within the embryo. These internal cells are the ones that will go on to form all of the cells of the body while the remaining outer cells go on to form other tissues such as the placenta.  For many years, researchers theorised that the internal cells adopt their position through a special process of cell division, however, due to technological limitations this had never actually been shown.

Now, researchers from the Monash University, University of Buenos Aires and Australian Regenerative Medicine Institute (ARMI) have developed a new non-invasive image processing technique which can visualise embryo formation. The team state that they were able to image, for the first time, the movement of all of the cells in living mammalian embryos as they develop under the microscope.  They go on to add the new study provides new insights into embryo formation and challenges the prevailing model of cell placement through division.  The opensource study is published in Developmental Cell.

Previous studies show that every cell in the human body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. It has been theorized that biomechanical forces might play a role in controlling cell allocation during early mammalian development.  Using their newly developed imaging methods, the researchers were able to demonstrate that this model of embryo formation was incorrect.

In the current study new imaging techniques were able to see how the cells moved and changed shape over time as they were ‘pushed’ inside to form the internal mass.  Data findings showed that there are differences in the tension of the membranes of the cells and these differences are what determine which cells will move inside to form the body.

The lab then applied cutting-edge laser techniques to the mammalian embryo to determine what forces were acting on the cells to make them move inside the embryo.  Results showed that by altering the tension of the cells using lasers or genetic manipulations, researchers could change which cells move inside the embryo.  These findings offer future potential to make alterations to improve inter-cellular forces and cell formation.  The group go on to add that their results offer an attractive possibility where alterations to the inter-cellular forces could increase embryo viability leading to better IVF outcomes.

The team state that in the future, this approach could also help with embryo selection before the embryo is implanted back into the uterus to improve IVF success rates.   The group hypothesize that if they can combine their new image processing technique with non-harmful dyes that can label the membranes of human embryos, they may be able to evaluate embryos used in IVF and decide which ones to implant to have the best chance of success.

The researchers surmise that this breakthrough has important implications for IVF (in vitro fertilisation) treatments and pre-implantation genetic diagnosis (PGD).  For the future, work is underway to use this new custom image segmentation technology with non-invasive imaging approaches to see how human embryos used in IVF or pre-implantation genetic diagnosis (PGD) first organise their cells.

Source:  Monash University

 

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture.  Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo.  Plachta et al 2015.

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture. Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo. Plachta et al 2015.

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