Mapping the mouse body
When we say someone’s feathers are ruffled, we imply they are upset or agitated and that the natural state of feathers is smooth and unruffled. Many features of an animal’s body, such as feathers, scales, or hair, point in the same direction. Individual cells making up the body appear to sense direction, but the signals that provide cells with this “directional cue” remain poorly understood.
Maureen Cetera, an Assistant Professor at the University of Minnesota and Society for Developmental Biology member, authored a study in the journal Development suggesting that the answer might lie in the genome of a popular breed of domesticated mice found among the hobbyist mouse breeding community.
“We know a lot about how neighboring cells can communicate directional information to each other,” said Cetera, but “how that information can be transmitted across hundreds, or thousands of cells, so that they all know which direction to face” is unknown.
The collective sense of direction shared among sheets of cells, known as planar cell polarity (PCP), has implications that go deeper than the skin, affecting most organs. Individual cells establish PCP by sorting specific proteins to opposing sides of cell boundaries. Some of these proteins protrude from the cell and contact neighboring cells, allowing adjacent cells to share information and align their axes of polarity. This alignment influences the movement and directional growth of these cells and tissues.
When PCP is not properly established during human development, the results are devastating. “Mutations in essentially all PCP genes cause very severe, multi-system birth defects that are not survivable,” said John Wallingford, a Professor at the University of Texas who was not involved in the study. These defects range from lethal forms of spina bifida to limb deformities and present major public health challenges.
When it comes to studying PCP in the lab, Wallingford asserts that “scientists use the parts of animals that are easier to study,” such as the skin of mice. After a project with hairless mice hit a dead end, Cetera used a Google Image search to find mice with hair patterns possibly indicating a disruption to PCP.
rosette mouse mutant (Credit: Maureen Cetera)
“I found this fascinating image of this mouse that just had whorls in [the back] half of its body, which just did not make any sense to me,” said Cetera. She had stumbled across what is known among mouse breeding hobbyists as the rosette mutant.
Rather than simply having a bad hair day, rosette mice appear stylish. The smoothly aligned hairs in the front half of the mice give way to swirling hairs in the back half, mimicking crashing waves where they meet in the middle. Unlike previously studied PCP mutants, which often have randomly oriented hairs, the rosette mice seemed to retain the ability to align their hairs, albeit with a polarity reversal halfway down their bodies.
After posting on message boards, joining Facebook groups, and traveling to mouse shows, Cetera obtained a rosette mouse to breed in lab. “This approach of being able to communicate with the public…it’s a really cool way to get information,” said Cetera. Beyond data collection, she views her connection to the mouse breeding community as an important opportunity to involve the public in her research.
Comparing the genomes of 91 different mice, with and without disrupted hair patterning, Cetera’s team was able to identify a single mutation among billions of base pairs correlating with the rosette hair pattern. The mutation affected the protein Fzd6, which is typically inserted in the cell’s membrane to facilitate communication between neighboring cells.
This one genetic alteration could have cascading effects beginning in the developing embryo. The mutated Fzd6 protein no longer accumulated near the cell boundaries, and cells in the back half of the mouse appeared to be “flipped.” Cetera observed PCP proteins accumulating on the side of the cell opposite from where they normally would be found. Later, when groups of cells formed hair follicles, the cells with flipped axes physically rotated in opposite directions from cells that established normal PCP, changing the direction of hair growth.
While nothing about the mutant proves that Fzd6 is directly responsible for providing the directional cue that orients hair follicles, the rosette mice open doors for studying what that cue might be. Over the years, scientists have turned to fly wings, zebrafish nervous systems and now rosette mice to study PCP. Beyond the unique hair pattern, the connections between Cetera’s lab and the community promise to benefit science and the public for years to come.
Last Updated 02/05/2024