Research team discovers five microRNAs that control critical developmental processes

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A team of scientists led by Wei Yan, M.D., Ph.D., professor of physiology and cell biology at the School of Medicine, discovered that five microRNAs function as a group to control the proper formation of basal forebrain, ciliated epithelia in the trachea and the oviduct, as well as sperm in the testis. Ablation of these five microRNAs leads to perinatal mortality owing to feeding and breathing difficulties caused by underdeveloped forebrain, which is responsible for food-seeking ability, and a lack of cilia in the trachea, which are microscopic, finger-like projections sticking out from the surface of cells and responsible for airway cleansing. Survived mice are completely infertile, with male sterility caused by disrupted sperm production and female infertility due to cilia-less oviduct that cannot capture ovulated eggs.

This work has been published in Proceedings of the National Academy of Sciences on June 30, 2014.

"These conditions are very similar to human primary ciliary dyskinesia (PCD), a rare disease affecting around 25,000 people in the United States," said Yan.

PCD is a disorder characterized by chronic respiratory tract infections, infertility and in some cases abnormally positioned internal organs and hydrocephalic brain. It has been known that abnormal cilia formation and function are responsible for PCD. However, the underlying genetic and epigenetic causes remain largely unknown.

"Our study discovered that small noncoding RNAs are involved in PCD, and this finding opens up a new avenue towards developing novel diagnostic and therapeutic measures for these conditions," Yan concluded.


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