Researchers at Weill Cornell Medical College have shown that a common growth factor with a role in cell growth and metabolism, IGF-1, uses cilia, the hair-like structures on a cell's surface, to tell a cell when it is time to replicate rather than differentiate and transform into a new kind of cell.
The finding has implications for many diseases that result from either too much or too little cell division. For example, a condition known as microcephaly, which causes severely underdeveloped brains, is linked to genetic mutations that affect ciliary function, slowing the division of stem cells in the developing brain.
The investigators' work, which was led by Celine Yeh, a research assistant at Weill Cornell, was published on Aug. 15 in Developmental Cell and featured on the journal's cover.
"We show that the IGF-1 signals transmitted through cilia trigger the shortening of the cilia themselves, an event that primes cells to divide," said senior author Dr. Ching-Hwa Sung, a professor of cell biology in ophthalmology at Weill Cornell.
"Our findings might help to explain why mutations in genes associated with ciliary function and IGF-1 signaling have overlapping phenotypes," Dr. Sung said, noting microcephaly, dwarfism and extended lifespan as examples of such conditions.
The paper builds on Dr. Sung's lab's previous work, which identified a molecular chain of events leading to the expansion of neural stem cells in the brain.
The IGF-1 receptor, the researchers found, plays a role in this chain of events, and when IGF-1 cannot communicate with embryonic neural stem cells, their division slows, prompting early differentiation into neurons, which cannot divide any further.
"When cilia can no longer resorb in response to external signals such as IGF-1, cells can no longer divide in a timely manner, contributing to defective growth phenotypes. This may lead to pathological conditions such as microcephaly," Yeh said.
At the same time, however, cilia serve as gateways that keep cells from proliferating too quickly. "Withdrawal of the cilium from the cell's surface must occur before the cell is able to divide. The cilium is present also to ensure that proliferation does not occur too rapidly," Yeh said.
The investigators now plan to look at the way IGF-1 functions through cilia in other types of stem cells, including adult neural stem cells.