Scientists at the Georgia Institute of Technology have found that by
applying chemicals to manipulate genes in a developing embryo, they’ve been
able to change the brain of one type of cichlid fish to resemble that of
another. The researchers also discovered differences in the general
patterning of the brain very early in development before functional neurons
form in a process known as neurogenesis. This finding is at odds with a
well-held theory known as “late equals large.” The research appears in the
Proceedings of the National Academy of
Sciences.
In the mid 1990s, the hypothesis called “late equals large” was put forth to
explain the way brains evolve across species. The brain begins as a blank slate.
In early development, the anterior, or front, part of the brain is specified
from the posterior, or back, part. After that, neurogenesis occurs as precursor
cells mature to become neurons. These precursors can replicate endlessly, but
once they become functional neurons, replication ends. The later the switch
from precursors to mature neurons, the larger the brain, or brain region,
becomes. The “late equals large” model holds that the brains of different
species, for example humans vs. mice, are similar early in development and
differ because of the later process of neurogenesis.
“We found differences in the general patterning of the brain as early as 48
hours after fertilization, before neurogenesis begins,” said J. Todd Streelman,
associate professor in Georgia Tech’s School of Biology.
Streelman, Ph.D. student Jonathan Sylvester, and their colleagues studied
brain development in six species of cichlid from Lake
Malawi stock, three species from the rock-dwelling lineage and
three species of their sand-dwelling cousins.
“We repeated our tests from two to four days after fertilization and found
that sand–dwelling cichlids exhibited a larger expression domain of the gene
wnt1, known to be an important factor in the development of the posterior
brain. This correlates with a larger thalamus, a posterior forebrain structure
used in the processing of vision,” said Sylvester.
The sand-dwelling cichlids use their vision to detect plankton prey, so
their brains are heavily devoted to integrating visual signals. However, the
rock-dwelling species feed by scraping algae from rocks and possess larger
cerebra, or telencephala, perhaps to aid in navigating their complex 3D
environments.
“The genomes of these species are very similar,” said Streelman, “almost as
similar as those of any two humans, and yet their brains vary as much as some
mammal groups, one from each other.”
Most of the data supporting the “late equals large” hypothesis hasn’t been
drawn from species that are as closely related as these cichlids, added
Streelman.
“Among primates, for example, most of the links between species have been
severed long ago. So, it is difficult to study developmental patterning because
subtle differences are often confounded by large differences in brain size,”
said Streelman.
In another part of the study, the team wanted to see if they could use
chemicals to change the patterns of gene expression and hence the brain
development of the embryos. Could they, in fact, alter the brain of a
rock-dwelling embryo to that of a sand-dwelling embryo? Turns out they could.
Sylvester treated the embryos with lithium chloride for three to five hours
during an early stage of anterior-posterior patterning. After treatment, he
returned the embryos to fish water and then took samples for study at different
developmental stages. He found that each time he checked, treatment with
lithium chloride up-regulated Wnt signaling, which led to a reallocation of
brain precursors to the posterior thalamus.
“Neurogenesis is still a very important process in brain development and
evolution,” said Streelman. “We’ve just shown that there are differences in the
developmental process much earlier than previously suspected and that these
changes are also relevant for brain diversity.”
“We’re interested in what these early differences have to say about early
behavior,” said Streelman. “Because if we think in terms of the ‘late equals
large’ model, it means that early in development, brains don’t differ that
much. But now that we know species possess divergent brains early on, we can
begin to assess how early behaviors may differ as well.”
Other members of the team include former Georgia Tech undergradate Constance
Rich, current Biology PhD candidate Eddie Loh, former post-doc toral fellow in
Streelman’s lab Gareth Fraser and Moira van Staaden from Bowling Green
University. The research was supported by funding from the National Science
Foundation, National Institutes of Health and the Alfred P. Sloan Foundation.
SOURCE
