By Andrea Yan and Henry Sun
Michael Barresi, a Professor of Biological Sciences at Smith College, was the speaker for the Biology Monday Seminar on December 4th. A prominent developmental biologist specializing in the development of vertebrae brains, he is a co-author of the widely-used textbook Developmental Biology. In his talk, he guided us through the process of building a brain—from the making of the cells to how they arrange themselves into the anatomical structure of the brain we know so well.
Barresi first introduced us to radial glia cells (RGC). RGCs are very important materials in building the brain; they influence brain development by providing a scaffold for the shape and locations of different parts of the brain. In order to develop a better understanding of these essential cells, the Barresi lab chose to study RGCs in zebrafish because of their easy accessibility, short (24h) development time, transparency, and the fact that zebrafish RGCs function the same ways they do in humans. In order to determine RGC’s role in forming new neurons in the spine, the lab developed transgenic reporters (genes that produce bioluminescent proteins) that make RGCs light up with fluorescence. As RG stem cells are capable of maturing into other kinds of more specialized cells, the lab tested that the fluorescent genes were still in those mature cells. Now that the lab understood that RGCs could grow into those specific types of cells, they wanted to see if perhaps other stem cells could also produce those same types of cells, in order to see if RGCs are necessary for them to form. In order to do this, the researchers expressed a neurotoxin that killed off RGCs cells to see which neural cells would remain. After finding significantly fewer cells in this treatment group compared to the control, Barresi’s team concluded that RGCs are the most important stem cells for spinal cord development.
Now that Barresi established a mechanism through which cells are made in the brain, he guided us to the next step in building a brain: communication and connecting cells. In the zebrafish brain, this is done through commissures, which are axons (the ethernet cable of neurons) that cross over hemispheres. In addition to connecting cells, we must properly position cells to ensure adequate development of the nervous system. This placement is done through the expression of the Sonic Hedgehog (SHH) protein. (When the SSH gene is faulty, the embryo grows spikes in its skin, resembling Sonic the Hedgehog, leading to its name.) SHH’s role is essentially to guide the commissures into their proper places. We now have a full picture of brain development from cell formation to the connections of cells to the positioning of the cells.
Then, Professor Barresi introduced the audience to his favorite cell–the neural crest cell (NCC), which creates bones. What’s so fascinating about these cells is that they are formed as a neural tube forms in the early stages of development, after which they migrate away from the spinal cord, never to return again. However, there has been a recent hypothesis that NCCs do actually migrate back to the spinal cord and contribute to forebrain development. RGCs actually serve as a barrier to NCC migration, being “traffic guides” and creating boundaries, and there is only a short moment in time where NCCs can get past the barrier to the spinal cord.
Looking ahead, Barresi hopes to draw connections between zebrafish and the pygmy zebra octopus. However, due to complications acquiring these specimens, the lab has been using the Hummingbird bobtail squid as a model due to their small size and ability to produce abundant offspring. The new model may provide greater insight into embryonic development than the previously used zebrafish models.