Single-cell uniparental disomies and mother-offspring interaction: a comparative study

Genomic imprinting refers to an epigenetic phenomenon where a limited number of genes are expressed differently, depending on whether they are maternally or paternally inherited. This process has been found to play a crucial role in shaping mouse phenotype, from placental formation to social and non-social behavioral traits. However, the exact mechanisms by which imprinting affects brain development and function are not fully understood yet. In this study, the specific effects of uniparental disomy (UPD) on brain development and functionality have been investigated. To do this, a mouse model called Mosaic Analysis with Double Markers (MADM), which allows to produce maternal and paternal UPD cell populations within the brain, was used. By in silico enrichment analysis, chromosomes 2, 7, and 12 appear to be enriched in imprinted and behaviorally relevant genes, with different effects on post-natal development. Specifically, MADM2, 7, and 12 present specific ultrasonic vocalization profiles, with MADM7 showing also changes in body weight. Furthermore, the localization of disomic cells in the adult brain was also characterized: Ch.12 disomic cells appear to be enriched in the thalamic ventroposteromedial nucleus (VPM) and hypothalamic arcuate nucleus (Arc), with a biased maternal vs paternal UPD cell distribution. Finally, the effect of Ch.12 disomic cell distribution on the adult mouse behavior was investigated, showing changes in the ultrasonic vocalizations profile and altered maternal attachment of pups born from MADM12 disomic mothers. These findings suggest that imprinted genes on different mouse chromosomes have different roles in postnatal development and participate in the formation of both young and adult mouse behaviors. Overall, this study sheds light on the role of genomic imprinting in brain development and function.