Uncovering the genetics of skeletal muscle growth and regeneration

March 8, 2018, Brigham and Women's Hospital
Zebrafish larvae with intact skeletal muscle structure and function (top) and impaired skeletal muscle structure (as seen with reduced birefringence, right panel) and function due to loss of Ddx27 (bottom). Credit: Vandana Gupta, Brigham and Women's Hospital

Skeletal muscle has a remarkable capacity to regenerate - a capacity that is diminished in many skeletal muscle diseases and aging. To investigate the mechanism behind skeletal muscle growth and regeneration, researchers from Brigham and Women's Hospital bombarded zebrafish with chemical mutagen and screened for larvae with defective skeletal muscle structure. Using genetic mapping, they found that zebrafish larvae with a mutation in DDX27 showed reduced muscle growth and impaired regeneration. Their results are published in PLOS Genetics.

"A major hindrance in the development of effective therapies for skeletal muscle diseases thus far has been a lack of understanding of the biological processes that promote and repair," said corresponding author Vandana Gupta, PhD, of the Division of Genetics at BWH. "Our study is one of the first efforts to provide specificity to the processes controlling in muscles, which will hopefully allow for the development of effective targeted treatments for skeletal muscle diseases."

Loss of is a debilitating feature that is a common manifestation of a wide array of diseases, and leads to reduced muscle function and increased morbidity and mortality. Maintenance of skeletal mass relies on a dynamic balance between protein synthesis and degradation. A number of conditions such as myopathies, sarcopenia, cancer cachexia, disuse atrophy, sepsis and chronic kidney diseases lead to a disruption of this balance in favor of reduced protein synthesis.

The researchers discovered that DDX27 is involved in ribosome biogenesis and protein synthesis in skeletal muscle. Loss of DDX27 affects the function of skeletal muscle by disrupting the regulation and production of proteins that are crucial for . Looking ahead the researchers hope to further explore the mechanism by which protein synthesis is changed in different disease conditions and develop approaches to target DDX27 regulated pathways to restore muscle growth and regeneration in skeletal muscle disorders.

"If we can promote muscle growth in patients with disorders, we would be able to restore and mobility in these patients, and reducing morbidity," said Gupta. "Our study is just the beginning of an effort to develop regenerative therapies for myopathies that could have a wide impact in a large patient population."

Explore further: From black hat to white hat: Findings tip assumptions about TAK1 in muscle growth

More information: Alexis H Bennett et al. "RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes" PLOS Genetics DOI: doi.org/10.1101/125484

Related Stories

From black hat to white hat: Findings tip assumptions about TAK1 in muscle growth

February 8, 2018
Among researchers exploring the mechanisms of muscle growth and health, there have been certain conceptions about the role of the signaling protein, transforming growth factor-ß-activated kinase 1 (TAK1). Convention was ...

Keratin hydrogels show significant potential to regenerate lost muscle tissue and function

April 27, 2017
The use of human hair-derived keratin biomaterials to regenerate skeletal muscle has shown promise in new research that documents significant increases in both new muscle tissue formation and muscle function among mouse models ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

Putting a 'HEX' on muscle regeneration

October 1, 2012
A complex genetic regulatory network mediates the regeneration of adult skeletal muscles. In this issue of the Journal of Clinical Investigation, researchers at the State University of New York Downstate Medical Center in ...

Menopause and estrogen affect muscle function

October 3, 2017
According to a study conducted at the University of Jyväskylä, estrogen acts as a regulator of muscle energy metabolism and muscle cell viability. Menopause leads to the cessation of ovarian estrogen production concurrent ...

Recommended for you

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

Deep data dive helps predict cerebral palsy

June 21, 2018
When University of Delaware molecular biologist Adam Marsh was studying the DNA of worms living in Antarctica's frigid seas to understand how the organisms managed to survive—and thrive—in the extremely harsh polar environment, ...

Genetic variation in progesterone receptor tied to prematurity risk, study finds

June 21, 2018
Humans have unexpectedly high genetic variation in the receptor for a key pregnancy-maintaining hormone, according to research led by scientists at the Stanford University School of Medicine. The finding may help explain ...

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.