An Organelle With ‘Interesting’ Potential

Published March 2019 | Developmental Biology

The path to understanding cilia, once thought to be vestigial, has traversed at least 112 years of research—a legacy now bolstered by a review article that describes the hair-like organelle's role in signal transduction across several molecular pathways that impact human development and disease.

The article links mutations that affect cilia transduction capabilities to conditions that range from disfigurement to lethal effects, including neural tube defects, limb deformities, the appearance of extra digits, loss of the tongue, salivary gland defects, nasal-facial deformities, bilateral cleft palate and later-life polycystic kidney disease.

A team led by first author Kelsey Elliott and senior author Samantha Brugmann, PhD, describes cilia as “interesting organelles” with potential for targeted therapies if researchers can better understand the basic mechanisms of cilia-dependent signal transduction across varied molecular pathways.

The article notes that cilium sits at the intersection of molecular cues and cellular processes including proliferation, migration, patterning and mechanosensation throughout embryonic development, organogenesis and into adulthood.

“One of our issues is that cilia are ubiquitous throughout the body,” Brugmann says. “That speaks to their importance, but it also speaks to the challenges of developing targeted therapies that can address ciliopathies without triggering or interfering with normal pathways elsewhere.” Some cancers and tumors are ciliated, her study points out, while others are not.

Further research, she says, must address existing controversies about the intricacies of cilium functioning, the degree of heterogeneity among primary cilia, even those extending from a single tissue, and whether primary cilia are “tunable” organelles that can increase or decrease sensitivity to some signaling pathways.