The newest installment of Science Savvy Column is out in this Friday’s Quest! If you’re part of the Reed College Community, you can always thumb through a print copy and find our column, but you can also read it online…by clicking here. If you want to read the research article featured in this week’s Science Savvy, you can download it here. You can also read the full, uncut version of the article (complete with great analogies and metaphors) below.
How Cellular Conversations Shape Embryonic Development – The Full Version
by Emily Crotteau and Colin Townes-Anderson
Have you ever wondered why you don’t have more than two eyes or why they’re on your face instead of the top of your head? During early embryonic development, a process called cell-to-cell signaling ensures that two, properly positioned eyes are formed. At first, the cells destined to be your eyes are indistinguishable from other cells in the developing brain. Then, in response to specific changes in their environment, the future eye cells start to express different genes than their neighbors and even start to move differently. Defects in the early events that distinguish eye cells from other brain cells give rise to a wide variety of congenital diseases including anopthalmia (lack of eyes), micropthalmia (tiny eyes), and cyclopia (a single eye). To understand the molecular basis for these diseases, scientists turn to basic biology, investigating the mechanisms that pattern and shape the embryonic brain.
The zebrafish, a small tropical fish available in local pet stores, is a surprisingly powerful a model for studying embryonic development. Humans and zebrafish share many of the same features during embryonic development. However, unlike humans, zebrafish eggs are fertilized externally, often in large clutch sizes (laying 300 or more eggs per week!), and they develop outside of the mother. Most importantly, the embryos are transparent, allowing researchers to capture how specific parts of the zebrafish brain grow and change throughout development.
In our Developmental Neurobiology Seminar, we recently discussed a paper that used zebrafish to examine the early events that lead to eye formation. In particular, the paper looked at how cells in the developing brain respond to molecular changes in their local environment to turn into eyes. Cells respond to environmental cues much like a row of dominoes topples over when you touch just one. Your finger knocking over the first domino is the environmental cue. The first domino is a receptor on the cell surface that receives the signal. The next dominos are a variety of messenger proteins, with the final domino symbolizing a protein that can bind DNA and influence gene expression. This chain reaction culminates in switching specific genes on or off. Changes in gene expression are a normal part of embryonic development, patterning the embryo so that cells that make up eyes, ears and brain end up in the right place in the adult organism.
The domino analogy explains how a single cell responds to a single extrinsic signal, but the embryo is a crowded place, with lots of cells and a plethora of signals. So how do cells make sense of all different extrinsic signals. One way to think about about cell-to-cell signaling is to think about what happens when you try to converse with a friend over the din of a crowded concert venue. Based on the proximity and volume of the people around you, you’ll hear some things clearly, while others will be drowned out. Some of what you hear might inspire you to start talking, move around, or help you coordinate activities with others. Among cells, the principle is the same, but instead of volume, the relative concentration of signals affects how they are interpreted. Furthermore, by expressing specific receptors on their surfaces, cells have ‘selective hearing’, so only certain signals are picked up. Cell ‘behavior’ results from the combined effects of the type and intensity of the signals they receive. One category of ‘behavior’ is the creation, or synthesis, of proteins from genes, resulting in the overall gene expression pattern of the cell. Scientists can ‘listen in’ on cellular conversations by detecting gene expression patterns with colorful chemical markers.
In 2005 , a group of scientists ‘listened’ to the cellular conversations that cause a group of undifferentiated embryonic zebrafish cells to begin to identify as “eye”. The authors were interested in the interactions between two signaling pathways. They conducted a series of experiments, varying the intensities of one signal or the other. They found a surprising result: when one of the signals was expressed in the absence of the other, the zebrafish embryos mapped out huge eyes. When the other signal was expressed in the absence of the first, eyes were absent or markedly reduced. When both signals were reduced, normal eye development occurred. Since the errors in eye specification occurred when the ratio of these two signals was altered, the researchers concluded that these two pathways have an antagonistic effect. Through the coordinated action of two signals, a group of undifferentiated cells are able to specify an eye that is neither too large, or too small (or nonexistent!), but just the right size.
After talking about this paper, our Development Neurobiology seminar got a real treat: we watched a recording of a Skype conversation between professor Kara Cerveny and the primary author of the paper, Florencia Cavodeassi. It’s not everyday that you get to hear a researcher reflect on her work and where it’s taken her. Since the publication of the paper we read, more information on how these two pathways work together in other contexts has come out. Florencia is continuing to study how these two pathways interact and is particularly interested in how these two signals affect genetic pathways and cell differentiation throughout the brain. After all, eyes are only one of the many chapters in the story of embryonic development, and there’s lots more to be discovered!
More information, including the article by Cavodeassi et al., 2005 and a interview with the lead scientist of the paper can be found here!