Proper cell–cell interactions are required for the cells of early embryos to develop normally

Pulling pipettes apart to gently separate early embryonic cells. Credit: 2013 C. Lorthongpanich et al.

Some 50 years have passed since scientists first proposed the so-called 'inside–outside model' of development, which holds that the inner cells of the early embryo eventually form all the definitive structures of the fetus, whereas the outer cells give rise to the placenta. Yet, the determinants of this developmental duality have remained elusive: are lineage decisions predetermined in the egg or is cell–cell contact needed to determine cell fate?

By physically separating cells in young mouse embryos, a team led by Barbara Knowles and Davor Solter from the A*STAR Institute of Medical Biology has definitively shown that extensive cell–cell interactions are required for proper lineage commitment.

After five rounds of cell division, a fertilized egg reaches the 32-cell stage. Chanchao Lorthongpanich, a postdoctoral fellow in the Knowles–Solter laboratory, mechanically separated cells at this and prior stages and then cultured the cells individually (see image). With her colleagues, she then measured the gene expression profiles of the separated cells. They showed that the pattern was out of sync with normal development, owing to the lack of proper cell–cell contact and the associated positional information that it confers.

Each of the cells, known as blastomeres, failed to display gene markers characteristic of either the inner cell mass—the part of the embryo that gives rise to the fetus proper—or the nourishing trophectoderm, the precursor to the placenta. However, the researchers observed a tendency toward 'trophectoderm-like' expression consistent with cells receiving an 'outside' signal. Furthermore, when the researchers reassembled the cells, they could not organize themselves into the multiple tissue layers needed for proper development.

"In the absence of structure and the clues provided by it, haphazard and incoherent gene expression is coupled with loss of lineage determination," says Solter, who is now working to determine the exact cues by which cell–cell interactions lead to proper development. This process is reversible for a short time, but the subsequent loss of proper signals results in permanent damage to the blastomeres, according to Solter.

In addition to providing insights into the basic biology of mammalian development, the results could have important implications for human reproductive medicine. Currently, embryo screening techniques to test for genetic diseases require destroying one or two cells from the embryo at the eight-cell stage. Since the fate of blastomeres is determined by positional cues, rather than any predetermined fate, such diagnostic testing is unlikely to result in fetal malformation, Solter notes.

More information: Lorthongpanich, C. et al. Developmental fate and lineage commitment of singled mouse blastomeres. Development 139, 3722–3731 (2012). dev.biologists.org/content/139/20/3722.abstract

Journal reference: Development

Provided by Agency for Science, Technology and Research (A*STAR), Singapore

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Computational study of ionic liquids illuminates detailed CO2 interactions

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Computational study of ionic liquids illuminates detailed CO2 interactions

The ?2 and ?1-CT structures of the acetate-CO2 complex.

Ionic liquids (ILs), which can be thought of as salts that are molten at room temperature, are being studied for use as part of CO2 adsorption and/or separation technologies. These applications depend on having strong interactions between the CO2 and the ions of the IL. In order for significant advances to occur in this area of research, the interaction between the CO2 and each IL must be understood and described with accuracy. Computational methods are used to describe these interactions on a molecular level.

National Energy Technology Laboratory scientist Jan Steckel has used a variety of methods to elucidate the complex nature of the interactions between CO2 and acetate ion. The results of this study were published recently in the Journal of Physical Chemistry A. The acetate ion was chosen because it is representative of the anions used in many ILs currently under investigation as CO2 sorbents or as part of a separation technology.

Dr. Steckel has shown that the acetate-CO2 potential energy surface is very complex. Eight energy minima, representing the most stable configurations, were located and characterized using computational methods that apply first-principles molecular orbital calculations to obtain an accurate description of these interactions at the molecular level.

The most stable structure is denoted ?2, (eta 2) where the CO2 interacts with both oxygen atoms of the acetate. This complex structure is predicted to have a binding energy of -10.6 kcal/mol, a measure of stability. There are several other complexes with binding energies close to -8.5 kcal/mol, but of these, the ?1-CT complex (eta 1) is unique. This complex is notable because the CO2 is bent to about 140°, the C atoms of the CO2 are only 1.54 Å away from the O of acetate, and there is evidence of charge being transferred from the acetate to the CO2 upon complexation.

Using these interaction energies as benchmarks, it was possible to investigate the degree to which more affordable methods can describe these complexes. Unfortunately, many popular and affordable computational methods do not succeed in describing the ?1-CT complex accurately. This study helps to provide a clear understanding of the acetate-CO2 interaction and supplies previously missing energetic and structural benchmark data. However, another important contribution made by this work is the revelation that widely-used but less accurate methods fail to accurately describe this interaction.

Journal reference: Journal of Physical Chemistry A

Provided by US Department of Energy

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