New cellular mechanism behind congenital heart disease uncovered

Researchers have discovered a previously unknown cellular mechanism linked to congenital heart disease, which affects about two in every 100 newborns globally. The finding, published in PLOS Biology, identifies a new communication system on the cell surface crucial for proper heart formation during embryonic development. The mechanism operates within the primary cilium, a microscopic antenna on most cells, where three proteins—TAK1, TAB2, and PKA-Cα—form a signaling hub that guides stem cells in becoming heart muscle cells. Genetic alterations can disrupt this process, leading to heart defects, according to the University of Copenhagen study combining patient genetic data with zebrafish and mouse stem cell experiments. The researchers found the mechanism may also affect other organs, potentially explaining why some patients with syndromic congenital heart disease have defects in the brain, kidneys, and skeleton. This discovery could improve early identification and targeted treatments for various rare genetic diseases caused by ciliary dysfunction.