Faculty Research in the News
Danelle Devenport presents seminar on planar cell polarity
Danelle Devenport spoke to an audience of students and alumni on Friday afternoon about her work with planar cell polarity, a phenomenon which is responsible for assembling cells into highly specialized tissues by giving them position, identity, and orientation.
“The question all developmental biologists try to understand is how we go from an amorphous ball of cells in the early embryo into this complex adult organism made of billions of cells assembled into complex and specialized organs with specialized functions,” Devenport said.
Devenport explained some basics of developmental biology, explaining that gradients of signaling molecules inform cells of position and that transcription factors inform cells of identity.
“Once a cell knows roughly it’s position and who it is, it needs to know how to assemble into the right configuration. The molecules of this directional function are called planar cell polarity molecules,” Devenport said. “This is really the phenomenon that I’ve been interested in for the past several years.”
Devenport went on to explain research into planar cell polarity, which she completed partially while as a post-doctoral student at The Rockefeller University and partially here at Princeton University. She spoke about mammalia skin and hair follicules, establishment of planar cell polarity in skin, and the presence of planar cell polarity in other tissues.
“In order to know how skin cells get a sense of direction, we have to know when in development they acquire their ability to sense direction and how it is that hair follicles respond to this and point toward the head.”
Devenport tested whether this process of hair follicle formation occurred via differential growth rates of cells on either side of the follicle or if it occurred due to cell shape differences. She found that it is the latter that is true.
“Cells on the head side of the follicle form these triangular shapes but the cells on the tail side stay square. It seems that the physical change in cell shape is sufficient to tilt the follicle towards the head.”
Then, Devenport sought to understand where skin cells acquire this directional information.
“We removed skin before it was polarized and after it was polarized and asked what happens to overall polarity,” Devenport said. Devenport found that when cells were removed after polarity had occurred, hair follicle formation occurred as normal with cells angling. But cells that were removed prior to polarization did not angle; it was as if they had never been polarized.
“There is a critical window in development where the skin is receiving directional cues and it needs to be in an embryonic context to do so.”
Devenport also tested how cells might communicate polarization information. Skin was removed, rotated 180 degrees, and then replaced. After the site was healed, it was found that the hair follicles in the rotated portion of skin had completely reoriented such that they matched surrounding areas.
“Even at this stage, the hair follicles in the skin contain all the information to maintain polarity,” Devenport said. “It could still respond to new signals in the environment. There is some communication going on between the old skin and the new skin.”
The next step was to determine what genes are responsible for planar cell polarity. Devenport took cues from Drosophila genetics who have studied planar cell polarity of hairs on fly wings, examining genes identified by looking at flies with mutant patterns of hairs on their wings.
“These genes are highly conserved across evolution,” Devenport said. “It seems pretty much any multicellular organism has genes similar to these identified in flies.”
She created genetic mosaic animals to ask just how these planar cell polarity genes are allowing cells to communicate directional information. In Drosophila, Devenport demonstrated that cells with normal polarity genes that are adjacent to regions with mutant cells will angle toward the mutant region; their polarity is interrupted even though they themselves have wild type genes.
“That tells us that these genes propagate directional signals from cell to cell over a certain distance.”
Then Devenport and her colleagues wanted to see if this held true when considering hair follicles made of thousands of cells. She mixed embryonic cells with mutant planar cell polarity genes with wild type embryonic cells. Despite the presence of fully wild type follicles, all of the follicles pointed straight down instead of angling toward the head as is the wild type condition.
Since the planar cell polarity genes are known to encode transmembrane proteins, Devenport knew these proteins were perfectly poised to cue signals from cell to cell. She wanted to understand where these proteins exist in the skin and pass this signal along.
“Not surprisingly, we found that they are in developing hair follicles around the time that they get their tilt,” Devenport said. “But we also found that the protein is in basal cells surrounding the follicle.”
Devenport next using laser confocal microscopy to look at the distribution of these proteins in the plane of the epithelium. Proteins localized to the head and tail sides of cells, but not to the left and right sides. Using GFP tagged proteins, Devenport was able to determine which specific types of planar cell polarity proteins were on which face of the cells. Devenport suggested that the differential localization of proteins allows for directional communication and will be continuing to do research in this area here at Princeton.
Devenport emphasized that this work has important relevance for human health and disease, as proper polarity of ciliated cells allows for the proper movement of fluid within the body. Improper planar cell polarity in mice can also cause severe neural tube defects, heart defects, lung branching defects, pancreatic abnormalities, defective cilia, and limb patterning defects. Neural tube closure has been especially studied in humans. Human mutations in planar cell polarity genes have been associated with neural tube closure problems such as spina bifidia.
“Sometimes people do research because they are just fascinated by a biological phenomenon or problem, like the Drosophila geneticists who pioneered this field and had no idea that what they were studying would have such great implications for birth defects and human disease. Sometimes research is performed just out of curiosity, sometimes it’s to cure human disease. Both ways can help us identify really important aspects of human health and disease.”