The goal of this research was to understand the developmental mechanisms underlying species differences in the size of the whole brain and some specific brain regions. In previous research we had compared the growth rates of the brain and its major subdivisions across several species of birds. Based on these findings, we had proposed several hypotheses about the cellular and molecular mechanisms underlying key developmental differences between the studied species. We then tested these hypotheses in the current research. In addition, we manipulated brain development experimentally in chicken embryos, causing part of their brain to become abnormally large. 

One of our main accomplishments was the discovery of a species difference in embryonic gene expression – specifically a shift in the expression boundary between two genes involved in brain patterning – that explains why parrots have a proportionately larger forebrain than quail and other chicken-like birds. By shifting this boundary further back, parrots allocate more of their embryonic brain tissue to develop into forebrain, rather than some other brain region. This early head start in “territory size” ensures that parrots have an enlarged forebrain throughout development, including as adults. This finding confirmed our hypothesis and was published in the journal “Evolution.” Our study is only the second study to report that evolution may enlarge a brain region by shifting the expression boundaries of brain patterning genes. 

A second significant achievement was our discovery that brain precursor cells divide more rapidly at very early stages of embryonic development in chickens, compared to bobwhite quail, thereby giving the chicken brain a “head start” in terms of cell number. At later stages of development, cells in the two species divide at roughly equal rates. We had predicted these results from a careful comparison of brain growth rates between the two species (chicken and quail), but we were now able to confirm our hypothesis by measuring cell division rates at several stages of development in both species. We suspect that species differences in absolute brain size often arise from changes in early precursor proliferation rates, but this remains speculative, because our study is the first of its kind. It was published in the “Proceedings of the Royal Society.” 

Having gained insights into the kind of natural variation in brain and brain region size that exists across species, we began to manipulate brain development experimentally. Given that the molecule FGF2 had been shown in mammals to prolong proliferation of neuronal precursors, we injected FGF2 into young chicken embryos. If FGF2 prolongs proliferation also in chick embryos, then our manipulation should prolong brain growth in chickens and, thus, create chickens with enlarged brains. This is indeed what we observed, though the enlargement was limited to a specific brain region, namely the optic tectum (presumably because only this region has the requisite FGF2 receptors). By combining our FGF2 injections with additional experimental procedures, we were able to show that, as expected, FGF2 enlarges the optic tectum by prolonging the period over which tectal precursors proliferate (the longer and more often the precursors divide, the more cells you end up with). A small handful of similar studies have been performed in mammalian embryos, but ours is the first to work with birds and the first to find a change in optic tectum size. The results were published in the “Proceedings of the National Academy of Sciences” and  “PLoS One.” 

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