Nav: Home

Gladstone scientists identify single microRNA that controls how heart chambers form

October 27, 2008

SAN FRANCISCO, CA - October 27, 2008 - Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California San Francisco (UCSF) have identified a genetic factor critical to the formation of chambers in the developing heart. The discovery of the role of a microRNA called miR-138, could offer strategies for the treatment of congenital heart defects.

The heart is one of the first and most important organs to develop. In fact, embryos cannot survive long with a functioning heart. In vertebrates (animals with backbones), special cells form a heart tube; that tube loops back on itself to form the atrium and ventricle and the canal and valve that separates them. This requires a complicated sequence of genes turning on and off. MicroRNAs are very small RNAs of 20 to 25 nucleotides that regulate numerous gene functions. Approximately 650 human miRNAs are known, but only a few have yet been studied to determine what they actually do in a cell.

Researchers, led by Sarah Morton, an MD/PhD student at UCSF and GICD Director Deepak Srivastava MD, examined zebrafish, which are an ideal model system for understanding genetic functions. Zebrafish are small, reproduce fast, and are essentially transparent so that that events of heart formation can be studied while they are still alive. Yet many of their systems are quite similar to those of humans. For example, miR-138 is exactly the same in zebrafish and humans.

"What's interesting is that a single microRNA is responsible for setting up the distinct patterning of a developing heart into separate chambers," said Dr. Srivastava, senior author of the study. "Since many congenital heart defects involve abnormalities in the formation of the chambers, this is important information in finding ways of treating or avoiding those defects."

The GICD scientists reported in today's issue of the Proceedings of the National Academy of Sciences USA, that miR-138 is present in the zebrafish heart at specific times and in specific places in the developing heart. Furthermore, they showed that it is required to insure that the cardiac chambers develop properly. When the scientists used genetic engineering techniques to eliminate miR-138, cardiac function was disrupted, and the ventricles did not develop correctly, with the muscle precursor cells failing to mature properly.

"The miR-138 function was required during a discrete developmental window that occurred 24-34 hours after fertilization," said Sarah Morton. The team also showed that the miRNA controlled development by regulating numerous factors that function jointly to define the chambers, including a key enzyme that makes retinoic acid.
-end-
Dr. Paul Scherz co-led this study, which involved close interactions with Dr.Didier Stainier, a Professor at UCSF, Dr. Kimberly Cordes and Dr. Kathryn Ivey. It was supported by grants from the National Institutes of Health and the California Institute of Regenerative Medicine.

About the Gladstone Institutes

The J. David Gladstone Institutes, affiliated with the University of California, San Francisco (UCSF), is dedicated to the health and welfare of humankind through research into the causes and prevention of some of the world's most devastating diseases. Gladstone is comprised of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. More information can be found at www.gladstone.ucsf.edu.

Gladstone Institutes

Related Zebrafish Articles:

How do zebrafish get their stripes? New data analysis tool could provide an answer
A new mathematical tool developed at Brown could help scientists better understand how zebrafish get their stripes as well as other self-assembled patterns in nature.
Zebrafish teach researchers more about atrial fibrillation
Genetic research in zebrafish at the University of Copenhagen has surprised the researchers behind the study.
How decisions unfold in a zebrafish brain
Researchers were able to track the activity of each neuron in the entire brain of zebrafish larvae and reconstruct the unfolding of neuronal events as the animals repeatedly made 'left or right' choices in a behavioral experiment.
'Census' in the zebrafish's brain
Dresden scientists have succeeded in determining the number and type of newly formed neurons in zebrafish; practically conducting a 'census' in their brains.
Zebrafish 'avatars' can help decide who should receive radiotherapy treatment
To date, there is no method for clearly determining whether radiotherapy will be an effective treatment for individual cancer patients.
Special cells contribute to regenerate the heart in Zebrafish
It is already known that zebrafish can flexibly regenerate their hearts after injury.
Survival of the zebrafish: Mate, or flee?
*Researchers have found that when making decisions that are important to the species' survival, zebrafish choose to mate rather than to flee from a threat.
Zebrafish capture a 'window' on the cancer process
Cancer-related inflammation impacts significantly on cancer development and progression. New research has observed in zebrafish, for the first time, that inflammatory cells use weak spots or micro-perforations in the extracellular matrix barrier layer to access skin cancer cells.
How a zebrafish could help solve the mysteries of genetic brain disease
A close look at the rapidly developing zebrafish embryo is helping neuroscientists better understand the potential underpinnings of brain disorders, including autism and schizophrenia.
Zebrafish help unlock mystery of motor neurone disease
Scientists from the University of Sheffield have successfully created zebrafish that carry the complex genetic change known to cause the most common genetic form of motor neurone disease (MND).
More Zebrafish News and Zebrafish 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

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.