Research into the biological basis of human speech and language has been constrained by the limited availability of mammalian model systems that permit functional characterisation across the levels of gene, brain and behaviour. To address this, I developed a flexible transient transgenic toolkit for
Phyllostomus discolor, a mammalian vocal learner, to investigate the functions of the language-associated gene
FOXP2. I first identified viral delivery systems suitable for transgenesis in the bat brain and show that, while lentiviruses were ineffective in vivo, AAV5 produced strong and consistent transgene expression across multiple brain regions. Using this toolkit, I developed a novel
FoxP2 knock-in strategy and used it to examine transcriptomic effects of
FoxP2 overexpression in the adult bat cortex. Differential expression of immune-related genes, but not canonical
FOXP2 target pathways, suggest that viral response may obscure
FoxP2-dependent transcriptional changes in bats in vivo. In parallel, I designed CRISPR/Cas9 constructs that successfully disrupted
FOXP2 in vitro in both human and bat cells. However, these constructs did not produce consistent knockdown in vivo, indicating that
FoxP2 may be subject to robust regulatory control in the bat brain. Finally, I carried out comparative transcriptomic analyses across species, revealing that humans and P. discolor bats share striking diversity of
FoxP2 isoforms in the brain. These species variants of
FoxP2 also share conserved roles in neurodevelopment, learning and synaptic transmission. Together, these findings show that comparative investigation of a mammalian vocal learner can illuminate both conserved and species-specific aspects of
FOXP2 function. Furthermore, the development of a transient transgenic toolkit for a mammalian vocal learner will allow exploration of the functional consequences of
FOXP2 manipulation at the levels of gene, brain, and behaviour. A clear understanding of
FOXP2 mechanisms in the mammalian brain may ultimately shed light on the biological basis of human speech and language.
| Date of Award | 30 Jun 2026 |
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| Original language | English |
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| Awarding Institution | |
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| Supervisor | Sonja Vernes (Supervisor) |
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