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

Apr 10, 2013
Development: When fate hinges on cell–cell contact
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 , 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 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 proper—or the nourishing trophectoderm, the to the . 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– 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.

Explore further: In between red light and blue light: Researchers discover new functionality of molecular light switches

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

add to favorites email to friend print save as pdf

Related Stories

Study unlocks origins of blood stem cells

Dec 09, 2011

A research team led by Nancy Speck, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, has discovered a molecular marker for the immediate ...

Researcher explain how embryo fights retroviral infection

Jun 24, 2010

Some viruses insert themselves into the host's DNA during infection in a process called retroviral integration, causing several diseases, including AIDS and cancer, notes a Texas A&M researcher who specializes in fetal diseases. ...

Timing germ cell development

Mar 15, 2013

(Phys.org) —Scientists from the Friedrich Miescher Institute for Biomedical Research identify a novel mechanism in early germ cell development. They show how the chromatin modulator PRC1 coordinates the ...

Recommended for you

Scientists see how plants optimize their repair

7 hours ago

Researchers led by a Washington State University biologist have found the optimal mechanism by which plants heal the botanical equivalent of a bad sunburn. Their work, published in the Proceedings of the Na ...

Structure of an iron-transport protein revealed

13 hours ago

For the first time, the three dimensional structure of the protein that is essential for iron import into cells, has been elucidated. Biochemists of the University of Zurich have paved the way towards a better ...

Over-organizing repair cells set the stage for fibrosis

13 hours ago

The excessive activity of repair cells in the early stages of tissue recovery sets the stage for fibrosis by priming the activation of an important growth factor, according to a study in The Journal of Ce ...

User comments : 0