Dr.
Ann Campbell Burke and the Chick Lab
by Vanessa Carbonell
"How do we, as very temporal beings, wrestle with trying to understand the dimension of history that's so much bigger than ourselves?" This question seems to be the central dogma of Dr. Ann C. Burke, Wesleyan University's newest Biology faculty member. Dr. Burke studies embryology and evolutionary biology, using specific organisms as models in a quest to uncover the secrets of development and find the link between the scientifically minute and the historically all-enveloping. The essence of this link lies in the notion that the grand evolutionary changes of time are dictated by the minute biochemical actions of genes.
While Dr. Burke's current research deals with chick embryos and the very specific mechanisms of their development, her past work spans a much broader field of knowledge. She claims that her initial interest in evolutionary biology was sparked by a curiosity about our "enormous vast past." Indeed, Dr. Burke has attacked the mysteries of the past head-on, most prominently in her study of turtle shell morphology and her work with the relationship between birds and dinosaurs. Her knowledge of vertebrate morphology, combined with research that uses modern-day DNA technology, has led her to be the first author of more than a dozen scholarly publications in the last ten years alone.
Early in her career, Dr. Burke did extensive research involving the morphology and evolution of the turtle. In reading over her work in the biology journals, an amateur might get the sense that an awful lot of attention is being given to a seemingly insignificant area of the turtle's skeleton. However, a conversation with Dr. Burke revealed just what exactly it is that makes the turtle so amazing. She explains that turtles have "rearranged the basic units of their skeleton in a way that no other vertebrate animal has done." Many vertebrates have protective armor--alligators, dinosaurs, and armadillos, to name a few. But what makes these animals different from turtles is that "they haven't done any rearrangement of their skeleton. All they've done is elaborated the skin, essentially, on their back. But what turtles have done is specifically altered the relationship of their vertebrae and their ribs to their limb girdles in a way that is a complete reorganization compared to any other animals, including the ones they evolved from." That turtles stand alone among all of the armored vertebrates makes them a fascinating and enigmatic subject for research, both in the realm of developmental biology and in the study of evolution. Dr. Burke seems to approach the turtle question with the kind of curiosity that draws people to circus freak shows. "It's like a really neat trick," she says, "to stuff your shoulder blades inside your rib cage."
Even more interesting than the actual body plan of the turtle is it's mysterious emergence into the grand scheme of evolution. Scientists have yet to find any fossils that illustrate the gradual evolution of the shelled-turtle from its ancestors. According to Dr. Burke, "there aren't any missing links between turtles and their non-turtle ancestors that show us how that morphology might have evolved. So it's a really intriguing evolutionary problem of how this might have come about. And it's really difficult to think of any functional intermediates that could have gradually transformed a normal tetrapod into a turtle." It is "missing link" problems such as these that continually rack the brains of evolutionary biologists, and so it is not surprising that Dr. Burke later became involved in yet another mystery of the past: the connection between birds and dinosaurs.
Many paleontologists theorize that birds evolved from dinosaurs--in fact this theory is regarded as proven truth. However, there have always been skeptics who challenge this relationship, and most often their arguments have a strong scientific basis. The debate over bird origins often comes down to differences in the methods of assessing homology, the quality of similarity which determines whether two organisms had a common ancestor. Paleontologists assess homology using evidence from the fossil record, which can be analyzed in the form of a cladogram--a branched diagram illustrating how one organism evolves into many others. But Dr. Burke and other evolutionary biologists have since approached the problem from another direction: embryology. By manipulating and comparing embryos of live species, scientists can collect data not available in the fossil record.
It
was Dr. Burke's embryological data that resulted in a paper
published in the journal Science in 1997. The paper,
entitled "Developmental Patterns and the Indentification of
Homologies in the Avian Hand," presented evidence collected from
the alligator, the primitive reptile Chrysemys, and the chick, all
three of which are ancestrally related. The crux of the debate
lies in how bird wing digits are numbered; since birds show only
three digits, but are theorized to have descended from dinosaurs
with five digits, the bird digits could be thought of as the
first, second, and third dinosaur digits, or as the second, third,
and fourth dinosaur digits. Dr. Burke uses embryological data to
argue that bird digits should be numbered II, III, IV, and her
argument sheds some doubt on the previous theory of the dinosaur
origins of birds. The discrepancy is particularly striking when
one considers the primitive dinosaur Herrarasaurus, which has
digits numbered I, II, III, x, x, with the last two digits being
vestigial. If bird digits are labeled II, III, IV, then birds
could not have descended from Herrarasaurus. According to a
commentary written by Richard Hinchliffe in that same issue of
Science, Dr. Burke's work is "the most important barrier to
belief in the dinosaur-origin orthodoxy." Nonetheless, Dr. Burke
seems to shrug off the implications of her work with modesty,
claiming "the relationship between birds and dinosaurs is probably
as intimate as most of the dinosaur people say, in that birds are
dinosaurs. . . . They know a lot more about the organisms than I
do. . . . And I think that somehow, in this case, both things must
be true&endash;&endash;that birds probably are dinosaurs,
but that bird digits are still numbered II, III, IV as opposed to
I, II, III."
Moving from the prehistoric to the futuristic, Dr. Burke's most recent research has centered around the role of Hox genes in development. Vertebrates have four clusters of Hox genes (A, B, C, and D), and different combinations of genes in these four clusters regulate development. Although studying the role of a certain gene is often a very specialized type of science, involving biochemical nuances invisible even with a microscope, it is really the most efficient way to study large-scale science, as most of evolution is dictated by genetics. "During evolution," Dr. Burke explains, "the only thing that's handed down between a parent and its offspring are its genes. And we know that the genes are able to produce all of the morphologies we see in the adult organism. They don't do it in a simple linear fashion, by any means; it's a very very complicated process." The genes most relevant to developmental biology are regulatory genes, which essentially tell other genes what to do. The Hox genes fall into this category, and they are directly related to morphology. "Just looking at the patterning of the axis from anterior to posterior, the Hox genes, if manipulated, can cause really pronounced or profound changes in the identity of the individual units along the axis. So this gives us a way of making a direct line between the genotype, which we know is the unit of inheritance, and the phenotype, which we know is generally the unit of selection, in an evolutionary sense. So understanding how morphology evolves over time can be tracked down to the role of regulatory genes in generating morphological patterns."
Dr.
Burke currently has a grant from the National Institutes of Health
to study the chick as a model system, specifically analyzing the
role of Hox genes in development. When the chick embryo is very
young, and still made up of just a few types of cells, each cell
is essentially just a copy of the others around it. But when the
cell populations begin to multiply significantly, certain cells
become designated to form tissue, muscle, bone, organs, etc.
Scientists are fairly sure that Hox genes play a role in
orchestrating some of these differences, and in ensuring that the
chick develops in more or less the same way as all other chicks.
Dr. Burke is particularly concerned with the development of the
axial (backbone) and apendicular (limbs) skeletons. Early in
development, small balls of tissue called somites form on both
sides of the embryo's midline, and eventually these somites will
grow into all of the vertebrae, ribs, and striated muscle in the
body. The question is how this tissue "knows" whether to become,
for example, neck bones on the anterior end of the skeleton, or
tail muscle on the posterior end.
To solve these mysteries of development, Dr. Burke tests hypothetical situations of morphology using microscopic surgeries. By first manipulating the embryo to change the course of development, letting it grow naturally for a short time, and then testing gene expression, she can begin to understand the patterns that govern Hox gene expression. For example, "if you move thoracic (rib-cage) level somites [balls of tissue] out of the trunk, and implant them in a region that is going to become neck, you'll get ribs in the neck, and vice versa, if you take cervical somites and put them in the thorax, you'll get a section of that thorax that is missing ribs."
In addition to the microsurgeries, Dr. Burke is also using the misexpression of genes to study development. By inserting a gene of interest into a retrovirus, and then delivering that retrovirus to a certain part of the tissue at a certain time, she can observe how a pattern-forming gene works in an area which would not normally have that gene at all, or at a time when that gene would not normally be expressed. Today's increasing bank of knowledge about genetics is certainly making this process more efficient, as many gene sequences can be obtained on the internet.
Dr.
Burke's lab will soon be using these same retroviral genetics
techniques to analyze the lineage of different cells in the chick
embryo. The retrovirus will deliver identifying "tags" into a
number of cells, and later "fish" them out. The genetic makeup of
the cells can then be studied to determine whether two cells are
clonally related--meaning they descended from the same cell at
some earlier point. This type of lineage study could have
interesting implications when applied to the shoulder blades
(scapula) of mammals and birds. The bird scapula is formed from
two different subsets of cells, whereas scientists are not sure
exactly what set of cells forms the scapula of mammals. Along the
same lines, the bird scapula is relatively long, and attached to
muscle that is used for flight, whereas the human scapula is
relatively short. Dr. Burke hypothesizes that an evolutionary
change affected the cell differentiation fate of these early
somites in birds, causing cells that originally formed muscle to
instead form bone in mammals. This hypothesis will be easy to test
using the retroviral "tag" method. If Dr. Burke is right, then
"those clones which end up in the scapula will overlap with cells
that are also forming muscle around the end of the scapula,
meaning that at an early stage of development a single cell of the
somite would eventually give rise to cells that would turn into
muscle, and also into bone."
Clearly, Dr. Burke has her hands full with research that seems to extend from the most technical aspects of DNA technology to the most broad-reaching mechanisms of evolution. Indeed, she studies organisms that range in size from a few celled-embryo to hulking dinosaurs, and changes that range in duration from a few minutes to hundreds of millions of years. And the future appears to hold even more interesting ventures; the grant from the NIH lasts until 2002, and Dr. Burke also has a grant pending from the National Science Foundation to comparatively study the role of Hox genes in the development of several organisms, perhaps including the alligator. Undoubtedly, we will continue to hear of exciting new ideas coming from the "chick lab."
Useful Internet Sites:
The Brooks/Cole Biology Resource Center
Harvard University's Department of Organismic and Evolutionary Biology
Page created: 4-25-00
Last updated: 5-4-00
Picture Sources:
chick embryo pictures courtesy of Development
alligator/avain hand graphic courtesy of Science