Ciliopathies are genetic disorders caused by defects in the structure and function of cilia, microtubule-based organelles present on the surface of almost every cell in the human body which play crucial roles in cell signaling. Ciliopathies present a wide range of often severe clinical symptoms, frequently affecting the head and face and leading to conditions such as cleft palate and micrognathia (an underdeveloped lower jaw that can impair feeding and breathing). In addition, the human ciliopathies include autosomal dominant polycystic kidney disease (ADPKD), a serious disease that affects approximately 600,000 in the United States, and autosomal recessive PKD, which is rare, affecting just 1 in 20,000 births, but also very serious. While we understand many of the genetic causes of human ciliopathies, they are only half the story: the question remains as to why, at a cellular level, defective cilia often cause developmental craniofacial abnormalities. Researchers have now discovered that ciliopathic micrognathia in an animal model results from abnormal skeletal differentiation and remodeling. The work from Christian Bonatto Paese, PhD, Evan Brooks, and others from Samantha Brugmann's (photo) (PhD) lab at the Cincinnati Children's Hospital Medical Center in the USA is published in Development. The article is titled “Ciliopathic Micrognathia Is Caused by Aberrant Skeletal Differentiation and Remodeling.” The researchers used the avian ta2 mutant as a model for Oral-Facial-Digital syndrome subtype 14 (OFD14), a rare human ciliopathy characterized by micrognathia. They observed defective formation of the jaw bone (mandible) at early stages of development in ta2 mutants. These defects correlated with unchecked progression through the cell cycle and over-proliferation in skeletal progenitor cells.
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