Captured on camera, published in Nature Cell Biology
For the first time, we have been able to watch as filopodia reach out and grab neighbouring cells, pulling them closer and elongating the cell membranes. Credit: EMBL Australia
When you were an embryo, just 8-cells large, your eight roundish cells did something they had never done before – something that would determine whether you survived or failed. They changed their shape.
The cells became elongated and compacted against each other, before returning to their rounded shape and dividing again and again.
It may seem simple enough, but this shaping process of cell elongation and compaction is essential for embryo success. When compaction does not occur, embryos tend not to survive. And the timing of compaction has been linked to success in IVF (in vitro fertilisation) treatments.
But how did these young, seemingly featureless cells undertake this vital shaping process?
Dr Nicolas Plachta and his team have found a new mechanism controlling the process. The EMBL Australia research team based at the Australian Regenerative Medicine Institute at Monash University used live imaging technology and microinjected fluorescent markers to capture the action in vivid images and video. The study used mouse embryos as a model for mammals including humans.
“Our images reveal arm-like structures called filopodia appearing on the outer membrane of approximately half of the cells during the 8-cell stage, and it is these filopodia that are responsible for contorting cell shape, and forming the embryo’s first tissue-like layers,” says Dr Juan Carlos Fierro-González, who is co-lead author of the paper with Dr Melanie White.
“For the first time, we have been able to watch as filopodia reach out and grab neighbouring cells, pulling them closer and elongating the cell membranes. We think that this enables the cells to effectively compact, as their new non-rounded shape makes the most of the available space.”
But the role of filopodia was made clearer upon seeing what happened next.
“We then saw the filopodia retract as they released their grip on neighbouring cells, allowing them to return to a somewhat rounded shape before they continued on their journey of cell division,” says Dr Fierro-González.
Dr Plachta and his team observed that cell division never occurred while filopodia were extended over the cells, but only once the filopodia had retracted. These observations have lead the researchers to believe that the filopodia provide the necessary surface tension to allow the cells to undergo expansion and compaction.
“Our findings reveal a completely unanticipated mechanism regulating the earliest stages of embryo development,” says Dr Nicolas Plachta, Leader of the Plachta Group. “In a sense, these arm-like filopodia are hugging the cells, squeezing them into shape.
“And we can apply that knowledge to human IVF treatments.”
Dr Plachta and his team are pioneering live imaging techniques to watch mouse embryos developing in real-time. And they are already working in partnership with the Monash School of Engineering to improve implantation success rates for human embryos.
“Now that we know what controls early development, we are designing non-invasive imaging approaches to see if human embryos used in IVF form normal filopodia and undergo normal compaction. This could help us choose which embryos should or shouldn’t be implanted back in the uterus,” says Dr Plachta.
EMBL Australia was created to capitalise on Australia’s associate membership of EMBL, the European Molecular Biology Laboratory, Europe’s flagship for the life sciences. EMBL Australia is an unincorporated joint venture between the eight Australian universities that form the Group of Eight and CSIRO. It is supported by the Australian government’s science infrastructure investments.
But how did these young, seemingly featureless cells undertake this vital shaping process?
Dr Nicolas Plachta and his team have found a new mechanism controlling the process. The EMBL Australia research team based at the Australian Regenerative Medicine Institute at Monash University used live imaging technology and microinjected fluorescent markers to capture the action in vivid images and video. The study used mouse embryos as a model for mammals including humans.
“Our images reveal arm-like structures called filopodia appearing on the outer membrane of some cells during the 8-cell stage, and it is these filopodia that are responsible for contorting cell shape, and forming the embryo’s first tissue-like layers,” says Dr Juan Carlos Fierro-González, who is co-lead author of the paper with Dr Melanie White.
“For the first time, we have been able to watch as filopodia reach out and grab neighbouring cells, pulling them closer and elongating the cell membranes. We think that this enables the cells to effectively compact, as their new non-rounded shape makes the most of the available space.”
But the role of filopodia was made clearer upon seeing what happened next.
“We then saw the filopodia retract as they released their grip on neighbouring cells, allowing them to return to a somewhat rounded shape before they continued on their journey of cell division,” says Dr Fierro-González.
Dr Plachta and his team observed that cell division never occurred while filopodia were extended over the cells, but only once the filopodia had retracted. These observations have lead the researchers to believe that the filopodia provide the necessary surface tension to allow the cells to undergo expansion and compaction.
“Our findings reveal a completely unanticipated mechanism regulating the earliest stages of embryo development,” says Dr Nicolas Plachta, Leader of the Plachta Group. “In a sense, these arm-like filopodia are hugging the cells, squeezing them into shape.
“And we can apply that knowledge to human IVF treatments.”
Dr Plachta and his team are pioneering live imaging techniques to watch mouse embryos developing in real-time. And they are already working in partnership with the Monash School of Engineering to improve implantation success rates for human embryos.
“Now that we know what controls early development, we are designing non-invasive imaging approaches to see if human embryos used in IVF form normal filopodia and undergo normal compaction. This could help us choose which embryos should or shouldn’t be implanted back in the uterus,” says Dr Plachta.
EMBL Australia was created to capitalise on Australia’s associate membership of EMBL, the European Molecular Biology Laboratory, Europe’s flagship for the life sciences. EMBL Australia is an unincorporated joint venture between the eight Australian universities that form the Group of Eight and CSIRO. It is supported by the Australian government’s science infrastructure investments.
Acknowledgements
We thank A. Yap, E. Jesudason, A. Fouras and J. Polo for comments on the manuscript; T. Bell for advice on laser ablations; S. Firth and I. Harper for help with imaging experiments; and R. Cheney, A. Yap and B. Henderson for sharing DNA constructs. N.P. is supported by ARC DP120104594 and DE120100794, NHMRC APP1052171 and Monash University Strategic and Interdisciplinary grants, and J.C.F-G. by Wenner-Gren Foundations and Swedish Society for Medical Research Postdoctoral Fellowships.
Author Contributions
J.C.F-G. and M.D.W. designed and performed the experiments. J.C.S. performed embryo microinjections and manipulations. N.P. supervised the project. J.C.F-G., M.D.W. and N.P. wrote the paper.
Dr Plachta will be available for interview via Skype, and other authors will be available via telephone.
For further information or to arrange an interview contact:
Courtney Karayannis, Senior Media Officer, Monash University, (03) 9903 4841 0408 508 454, courtney.karayannis@monash.edu
Laura Boland, Science in Public, (03) 9398 1416, 0408 166 426, laura@scienceinpublic.com.au