Alumnus Story: Derrick Glasco
Jan. 4, 2000
The Great Cell Migration: Understanding Facial Brachiomotor Neuron Migration
COLUMBIA, Mo. – The Arctic tern’s annual flight to and from the Antarctic, the North American monarch’s 3,000 mile round-trip flight, the seasonal movement of over one million wildebeest across the plains of the Serengeti: we all have our favorite great migrations. MU graduate student Derrick Glasco’s favorite is less well known but a lot closer to home.
All of us (all vertebrates, that is) are products of a great migration, a great cell migration. Embryonic development in animals begins with the single fertilized cell. This cell initially divides into a mass of very similar cells. Over the course of hours or days, those cells begin to differentiate, or distinguish themselves one from another: some become gut, some become muscle, and some become neurons. In the early part of embryonic development, many of these cells migrate into appropriate positions.
Differentiated neurons also migrate. In the central nervous system, the migration of several types of neurons from their birthplaces in the neural tube to their final destination in a different location of the brain is an important process. For example, migration of cortical interneurons is crucial for the formation of layers in the cortex (the outer part of the brain). In addition, the neurons of the olfactory bulb (a part of the brain involved in the perception of smells) are replenished throughout adult life by a constant stream of migrating neurons. This process of neuronal migration is, in Derrick’s eyes, one of the greatest migrations.
Derrick’s doctoral research focuses specifically on facial brachiomotor neurons. These neurons, which are located in the hindbrain, eventually become the facial nerves that innervate muscles involved in chewing, swallowing, and a variety of other facial movements. This set of neurons has become a model for studying how neuronal migration works because of its dynamic migration pathway. The hindbrain region of the neural tube is subdivided into several segments called rhombomeres. Facial brachiomotor neurons migrate caudally—that is, anterior to posterior—from rhombomere 4 into rhombomeres 5 and 6. According to Derrick, this is an impressive distance for a neuron to migrate.
Studies in zebrafish and other model organisms have shown that migration of the facial brachiomotor neurons is controlled by a specific genetic pathway, called the non-canonical Wnt/planar cell polarity (PCP) pathway. This pathway controls the polarity of cells and convergent extension movements or, in other words, the cell’s ability to point or orient itself in a particular direction. Dr. Anand Chandrasekhar, Derrick’s graduate mentor in Biology, has shown that the gene strabismus (stbm), which is one component of the Wnt/PCP pathway, is necessary for facial brachiomotor neuron migration in zebrafish; if you disrupt this gene, these neurons fail to migrate properly during early development.
“But does it have a similar function in mammals? That is what I’m trying to determine with my research,” says Derrick. “While we already know that these cells migrate in mammals, we wanted to see if genes of the PCP pathway regulate this process in mammals.”
To answer this question, Derrick is studying facial brachiomotor neurons in mice. The mouse is an ideal organism. Not only has facial brachiomotor neuron migration been studied intensively in mice but a mouse line with a mutation in Van gogh-like 2 (Vangl2), a homologue of the zebrafish stbm gene, already exists. His research would seem pretty straightforward if it were not for the fact that his mentor’s lab works exclusively with zebrafish.
“We didn’t have any mice. We didn’t have any mouse colonies. Nothing. Every protocol we had was zebrafish,” shares Derrick. “At the time, no one on campus was even working with mice at the embryonic level of development I was interested in.”
Somehow, this did not appear to be a deterrent to either Derrick or his mentor, Dr. Chandrasekhar.
“Anand sent me to a couple different places including Kansas City and Omaha to go work in other people’s labs to learn some of the techniques that I really had to learn,” continues Derrick.
Then Dr. Samuel Waters joined the Biology faculty and started working in the lab across from Derrick in MU’s Life Sciences Center. Although Dr. Waters’ research focuses on patterning and cell body placement in the hindbrain, he is working with mouse embryos at about the same stage of development as Derrick’s. He has become one of Derrick’s co-mentors.
Derrick’s research on mice is already confirming the findings in zebrafish. Mice with a mutation in one copy of Van gogh-like 2 (heterozygotes) show a migration defect in the facial brachiomotor neurons. Mice with mutations in both copies of this gene (homozygotes) show both migration defects as well as a pronounced neural tube development defect (i.e., an open neural tube). The fact that the heterozygous embryos don’t have a neural tube defect but do have a migratory defect is important: “It suggests that this protein probably has a novel function just for migration. Anand’s studies in zebrafish suggest that this function may, in fact, have its own pathway, one independent of the non-canonical Wnt/PCP pathway.”
Derrick is also working on characterizing an additional gene, Celsr1, in the non-canonical Wnt/PCP pathway that is also involved in migration of the facial brachiomotor neurons in mice. Celsr1, says Derrick, shows a very intriguing phenotype when one copy of the gene is disrupted: “A large number of the facial brachiomotor neurons migrate in a backward direction—rostrally instead of caudally!” Nowhere in the literature (zebrafish or mouse) has a phenotype like this ever been described. “In other mutants,” continues Derrick, “facial brachiomotor neurons either migrate or they don’t. There is not much in between. This is an exciting finding.”
Derrick expects that his research on characterizing Van gogh-like 2 and Celsr1 in mouse will help shed light on the non-canonical Wnt/PCP pathway specifically and neural migration in general.
The ability to choose his own path is what attracted Derrick to MUs Biology Graduate Program. Like many other graduate students, Derrick was not sure what he wanted to study in graduate school, so a graduate program with flexible course offerings and rotations was important to him. As it turns out, it took Derrick only one meeting with his mentor and one rotation to figure out what he wanted to do. When asked to comment on his future migrations, Derrick says that pathway is also unknown at the moment: “I really like teaching, and I really like bench work in the lab, so I’m looking into industry as well. But, you know, I’m really not sure.” Whatever he decides to do, he knows he will be well prepared for his journey.
Written By: Melody Kroll, MU Division of Biological Sciences
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