SUMMARY
Dopa decarboxylase (DDC) regulates the synthesis of monoaminergic neurotransmitters and is linked to psychiatric and metabolic disorders. Ddc exhibits complex genomic imprinting effects that have not been functionally studied. Here, we investigate different noncanonical imprinting effects at the cellular level with a focus on Ddc. Using allele-specific reporter mice, we found Ddc exhibits dominant expression of the maternal allele in subpopulations of cells in 14 of 52 brain regions, and dominant paternal allele expression in adrenal cell subpopulations. Null mutations in the maternal versus paternal Ddc alleles differentially affect offspring social, foraging and exploratory behaviors. Machine learning analyses of naturalistic foraging in Ddc-/+ and +/- offspring uncovered finite behavioral sequences controlled by the maternal versus paternal Ddc alleles. Additionally, parental Ddc genotype is revealed to affect behavior independent of offspring genotype. Thus, Ddc is a hub of maternal and paternal influence on behavior that mediates diverse imprinting and parental effects.
HIGHLIGHTS
Dopa decarboxylase (Ddc) allelic expression resolved at the cellular level
Cells differentially express maternal versus paternal Ddc alleles
Maternal and paternal Ddc alleles control distinct behavioral sequences
Parental Ddc genotype affects offspring independent of mutation transmission
eTOC Allelic reporter mice and machine learning analyses reveal dopa decarboxylase is affected by diverse imprinting and parental effects that shape finite behavioral sequences in sons and daughters.
Competing Interest Statement
A patent has been filed on the DeepFeats algorithm. C.G. is a co-founder of Storyline Health Inc., which is building artificial intelligence technologies for behavior analysis.
