A new study led by researcher Cedars-Sinai has discovered a gene that plays an important role in the biological pathway of embryonic development. The effect of the gene at the cellular level may explain why some children are born with physical abnormalities and why some adults develop diseases such as cancer. The findings are published in The nature of communication.
Human embryos develop through many complex cellular processes. Chemical reactions known as “signaling pathways” activate molecules in a cell to control its functions. For this study, researchers sought to better understand the so-called Hedgehog signaling pathway, which regulates human embryo growth but is also active in adulthood. They found that the gene Cnpy4may affect the ability of the cell to follow the Hedgehog pathway.
“There are several signaling pathways that are critical regulators of all biological processes that occur during development and are also involved in disease, so we want to understand how these pathways work,” said Ofir Klein, MD, co-author. research and CEO of Cedars-Sinai Guerin Children’s. “What we’ve identified here is a gene that is a very important modulator of the Hedgehog critical pathway.”
The researchers noticed that laboratory mouse embryos with the mutation in Cnpy4 the gene was born with polydactyly, a congenital defect that involves extra fingers or toes. Some of the mice also had abnormalities in the spine and ribs. Previous research has shown that changes in the Hedgehog pathway can cause these congenital malformations.
The team found that Cnpy4 the gene affects the level of lipids on the cell membrane or the area that separates the inner part of the cell from its external environment. Changes in lipid levels affect an important protein called Smoothened, which is a vital component of the Hedgehog pathway. Mice that were missing Cnpy4 had elevated levels of available cholesterol on cell membranes, causing Smoothened to signal more strongly. This led to hyperactivity pathway and uncontrolled generation of new cells.
“This pathway is one of the few that is central to human development,” said Klein, who holds the outstanding Department of Child Health of David and Meredith Kaplan in Cedars-Sinai. “And because the same pathways are affected by different disorders, we believe they may be a target for cancer treatment, which we know is related to the Hedgehog signal.”
Klein said they are developing drugs that affect function Cnpy4 the gene may provide new treatment options for diseases, including cancer.
Klein previously ran the Institute of Human Genetics at the University of California, San Francisco (UCSF), where he completed his studies and remains an adjunct professor. The co-author of the study is Natalia Yura, PhD, Associate Professor of Cellular and Molecular Pharmacology and a researcher at the Institute of Cardiovascular Research at UCSF.
Funding: The study is funded by the UCSF Sandler Program for Breakthrough Biomedical Research and the National Institute of Dental and Craniofacial Research under award numbers R01-DE028496 and R35-DE026602.
Source of history: