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Mutant Roundworms Might Shed Light on Causes of Ribosome Disorders

mutant c elegans700 2In a paper published in the journal Developmental Cell last month, researchers from The University of Texas at Austin gained insights into how tissues diversify during embryonic development. These initial findings may provide clues about the causes of ribosomopathies, human disorders involving ribosomes, the molecular machines within cells that produce proteins.

The paper was co-authored by Elif and Can Cenik, assistant professors in the Department of Molecular Biosciences. 

Embryos of the roundworm C. elegans inherit ribosomes from their mothers and also produce new ribosomes as they grow. To determine whether the new embryonic ribosomes are involved in tissue diversification during development, the researchers created and observed mutant strains of C. elegans which lack the ability to make new ribosomes. They found that the mutant C. elegans embryos were able to complete embryogenesis and became a fully differentiated larvae. In other words, making new embryonic ribosomes is not required for protein synthesis during embryogenesis. Inheriting maternal ribosomes is sufficient for tissue diversification and viable larvae. 

However, without the ability to make new ribosomes, postembryonic development is arrested and can’t progress past the beginning stages of the C. elegans life cycle. The researchers used a set of genetic tools to make mosaic embryos, where some of the cells of the embryo completely lack the capability of making new ribosomes and the rest of the cells are wild-type, or fully functional. After completing embryogenesis, these larvae failed to grow, meaning wild-type and mutant cells in the mosaic embryo were arrested in the same way. These results suggest a global checkpoint that regulates postembryonic development.

“In simple terms, when some cells of the embryo are not able to produce new ribosomes, it’s sufficient to inhibit wild-type normal cells from growing further,” Elif Cenik said. “This suggests the presence of factors that coordinate growth of different tissues or organs of an organism to conserve body plan. We don't know what these factors are but we have a great genetic system to discover them.”

This could help scientists better understand how ribosomopathies are inherited and why some people with the genes for the diseases experience no symptoms whereas some individuals are severely affected. Further, mosaic embryos could have in vitro fertilization (IVF) applications, because researchers can now use high-resolution sequencing to identify mosaic embryos before implantation. These embryos sometimes––but not always––result in developmental defects, and understanding the system that coordinates growth in mosaic embryos could help determine which will result in a normal birth.

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