Dopa decarboxylase is a genetic hub of parental control over offspring behavior

Abstract

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 or maternal allele expression in adrenal cell subpopulations. Maternal versus paternal Ddc allele null mutations 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. HIGHLIGHTSO_LIDopa decarboxylase (Ddc) allelic expression resolved at the cellular level C_LIO_LICells differentially express maternal versus paternal Ddc alleles C_LIO_LIMaternal and paternal Ddc alleles control distinct behavioral sequences C_LIO_LIParental Ddc genotype affects offspring independent of mutation transmission C_LI eTOCAllelic 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.