Nav: Home

MDC researchers discover new signaling pathway in embryonic development

March 10, 2015

During pregnancy, the mother supplies the fetus with nutrients and oxygen via the placenta. If placental development is impaired, this may lead to growth disorders of the embryo or to life-threatening diseases of the mother such as preeclampsia, a serious condition involving high blood pressure and increased urinary protein excretion. Now, Dr. Katharina Walentin and Professor Kai Schmidt-Ott of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered a new molecular signaling pathway which regulates the development of the placenta. Perturbations of this pathway in mice cause developmental defects of the placenta (Development 2015 142:1125-1136; doi:10.1242/dev.113829)*.

The study focused on the gene regulator grainyhead-like 2 (GRHL2), which the research group has been investigating for a several years. As Dr. Walentin and Professor Schmidt-Ott have now shown, this regulator plays a key role in the development of the placenta. In a previous study, Professor Schmidt-Ott and his team discovered that it regulates the differentiation of epithelial cells - they line the cavities and surfaces of structures throughout the body - in the mouse embryo.

In the current study, the researchers noted that GRHL2 is very active in the healthy placenta, especially in trophoblast cells, which are responsible for the development of the labyrinth. This placental labyrinth forms the interface between the blood circulation of the embryo and the mother. It ensures the exchange of nutrients and oxygen as well as the removal of embryonic metabolic end products. The trophoblast cells branch out to form the labyrinth, and they are accompanied by fetal blood vessels. Thereby, a large interface is created to facilitate the exchange of metabolites between mother and fetus.

In mice, when the researchers inactivated the gene regulator GRHL2 in the fetal part of the placenta and in the embryo, the development of the labyrinth was severely disrupted. In particular, the branching of the trophoblast cells and the migration of the fetal blood vessels into the placenta were impaired. When the researchers inactivated the gene regulator only outside the placenta in the embryo, the labyrinth developed normally. Using genome-wide analyses, the MDC researchers found that GRHL2 regulates a defined gene program. Components of this program are critically involved in the development of the placenta.

During their studies, which were funded by the German Research Foundation (DFG) and the Urological Research Foundation, the researchers additionally discovered that GRHL2 and its target genes also display activity in the human placenta. They hope that these findings could be significant for the understanding of developmental abnormalities of the placenta and related pregnancy disorders in humans.
-end-
*A Grhl2-dependent gene network controls trophoblast branching morphogenesis

Katharina Walentin,1,2 Christian Hinze,1,2 Max Werth,1,2,3 Nadine Haase,2 Saaket Varma,4 Robert Morell,5 Annekatrin Aue,1,2 Elisabeth Pötschke,1 David Warburton,4 Andong Qiu,3 Jonathan Barasch,3 Bettina Purfürst,1 Christoph Dieterich,6 Elena Popova1, Michael Bader1, Ralf Dechend,2 Anne Cathrine Staff,7 Zeliha Yesim Yurtdas,1,8,9 Ergin Kilic,10 and Kai M. Schmidt-Ott1,2,11,*

1Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.2Experimental and Clinical Research Center, a collaboration between the Max Delbrück Center and the Medical Faculty of the Charité, Robert-Rössle-Str. 10, 13125 Berlin, Germany. 3Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. 4Department of Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA. 5Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders (NIDCD)/National Institutes of Health (NIH), 5Research Court, Rockville, MD 20850, USA.6Bioinformatics, Max Planck Institute for Biology of Ageing, Robert-Koch-Str. 21, 50931 Cologne, Germany. 7Department of Gynecology and Obstetrics, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Kirkeveien 166, 0450 Oslo, Norway. 8Department of Urology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. 9Berlin Institute of Urologic Research, Berlin, Germany. 10Department of Pathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. 11Department of Nephrology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

A photo of the placenta of a mouse can be downloaded from the Internet at News: https://www.mdc-berlin.de/en

Contact:

Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10
13125 Berlin
Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/de

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Related Placenta Articles:

MicroRNA regulates process vital to placenta growth in early pregnancy
A study by University of South Florida Health (USF Health) researchers discovered how a very large human non-protein coding gene regulates epithelial-to-mesenchymal transition (EMT) -- a process that contributes to placental implantation during early pregnancy, as well as cancer progression and spread.
Bovine embryo completely regenerates placenta-forming cells
A calf was born from an embryo lacking cells which form a large part of the placenta, providing new insight into the regenerative capacity of mammalian embryos.
Study finds common cold virus can infect the placenta
For the first time, researchers have shown that a common cold virus can infect cells derived from human placentas, suggesting that it may be possible for the infection to pass from expectant mothers to their unborn children.
Placenta changes could mean male offspring of older moms more likely to develop heart problems
Changes occur in the placenta in older pregnant mothers leading to a greater likelihood of poor health in their male offspring, a study in rats has shown.
NIH-funded study: Placenta imaging method may aid diagnosis of pregnancy complications
A new imaging technique to track maternal blood flow to the placenta has the potential to help diagnose several common complications in early pregnancy, according to a study funded by the National Institutes of Health.
Placenta transit of an environmental estrogen
The human foetus is considered to be particularly sensitive to environmental contaminants.
Babies burdened by environmental estrogens in mothers' wombs
Early childhood life in the womb is particularly sensitive to the effects of environmental pollutants.
Placenta pathology may clarify racial disparities in preemie health outcomes
African-American infants are twice as likely to die in the first year of life than white infants, for reasons that are complex and not well understood.
New evidence supports the presence of microbes in the placenta
Researchers report visual evidence supporting the presence of bacteria within the microarchitecture of the placental tissue.
Drinking alcohol even at conception damages placenta development
Alcohol consumption during pregnancy can have disastrous consequences for the developing fetus, leading to low birth weight and fetal alcohol syndrome.
More Placenta News and Placenta Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.