Embryonic development involves temporal and spatial coordination of epigenetic processes,
which are exquisitely sensitive to environmental influences and can have life-long implications
for disease if disrupted. In this thesis, I examined the impact of gestational diet, specifically protein
restriction, on the expression of cyclin-dependent kinase inhibitor C1 (Cdkn1c), a gene that
is epigenetically regulated through genomic imprinting, during development and post-natally,
with an allele-specific bioluminescent reporter mouse model. I showed that in utero low protein
diet (LPD) exposure affects behaviour in adolescence and adulthood, through changes in the
dopamine system at a transcriptional, cellular and metabolic level. Sensitisation experiments
suggest that adult LPD mice are hypersensitive to cocaine, as they show increased locomotor
activity compared to controls, and increased stereotypy at higher doses. Adult LPD mice also
show hyperactivity and reduced anxiety, which are phenotypes frequently observed in hyperdopaminergic
mouse models. Adolescent LPD mice demonstrated impaired motor function, in
contrast to age-matched controls, based on open field and rotarod performance. However, I have
shown this deficit to be transient and resolved by adulthood. Juvenile and adult LPD-exposed
mice displayed a 25% increase in midbrain dopaminergic neuron numbers. Moreover, RNA
analysis from adult midbrains showed a downregulation of the gene that encodes dopamine
transporter (DAT) and upregulation of dopamine receptor 5 (D5) in LPD mice, with many
other dopamine-related genes unaffected. A pilot RNA-seq experiment on midbrain neuronal
nuclei identified 123 differentially expressed genes in LPD mice, affecting cholesterol synthesis
and markers linked to neurodegeneration and early-life stress. Lastly, μPET imaging revealed
elevated striatal dopamine synthesis capacity in adult LPD mice, recapitulating one of the
hallmarks of schizophrenia, and in accordance with reports of gestational exposure to famine
inferring increased susceptibility to schizophrenia. This work sheds light on consequences of
early-life adversity and epigenetic disruption on embryonic brain development, behaviour and
disease risk.