What do sperm, eyes, kidneys and lungs have in common? These radically different cells and organs all require properly functioning, hair-like cellular protrusions known as cilia to perform their chores.

When cilia are absent or defective in certain cells, human infertility, blindness, kidney disease and lung dysfunction can occur. So when UCSD biologists this spring discovered a number of key genes that humans, mice, fruit flies and roundworms all need to produce properly functioning cilia, they knew they were onto something big.

In a paper featured on the cover of the May 14 issue of the journal Cell, Charles Zuker, a professor of biology and of neurosciences, postdoctoral fellow Tomer Avidor-Reiss and their colleagues report the identification of some 40 genes that play a role in cilia formation. They also discovered that six genes are essential for the assembly of this cell structure. “If a cell doesn’t have all of them, it is unable to grow cilia,” Zuker says.

The discovery of these genes provides medical researchers with a critical new tool for diagnosing genetic diseases that involve cilia dysfunction and possibly for developing drugs that can minimize the effects of such dysfunctions.
“What was disconcerting about human cilia defects was that the disorders were not initially tied to cilia dysfunctions,
because the physiology of these diseases is so complex and broad,” Zuker says. “These people have problems with their retinas, lungs and kidneys. It’s only been in the last few years that scientists have understood the etiological basis of some of these human genetic disorders.”

Male infertility is probably the most commonly known result of a type of cilia dysfunction. In humans, sperm navigate toward the egg by propelling themselves with a type of cilia known as flagella. Defects in these whip-like cilia result in non-motile sperm and male infertility. Other widely known human cilia disorders include pulmonary diseases caused when respiratory cilia, which cleanse the lungs by sweeping mucous into the throat, are defective. Vision problems can also be caused by defective cilia in the eye’s photoreceptors.

In recent years, that list of disorders has grown as medical researchers discovered that many human genetic ailments affecting organs have their origin in the absence or dysfunction of cilia. These include polycystic kidney disease, the most common genetic cause of kidney failure; embryonic problems in the body’s right-left symmetry that cause organs to develop on the wrong side of the body; and Bardet-Biedel syndrome, a rare genetic disorder characterized by obesity, learning disabilities and eye and kidney problems.

“This will provide the basic foundation to understand how cilia form,” says Avidor-Reiss. “It is only recently that scientists began to realize that there are links between cilia dysfunction and a wide range of human genetic diseases. Now we have an exciting collection of candidate genes.”