The parenting hub of the hypothalamus is a focus of imprinted gene action

by Matthew J. Higgs, Anna E. Webberley, Alasdair J. Allan, Moaz Talat, Rosalind M. John, Anthony R. Isles

Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations responsible for controlling parental care, to test whether imprinted genes significantly converge to regulate parenting behaviour. Using single-cell RNA sequencing datasets, we identified a specific enrichment of imprinted gene expression in a recognised “parenting hub”, the galanin-expressing neurons of the preoptic area. We tested the validity of linking enriched expression in these neurons to function by focusing on MAGE family member L2(Magel2), an imprinted gene not previously linked to parenting behaviour. We confirmed expression ofMagel2 in the preoptic area galanin expressing neurons. We then examined the parenting behaviour ofMagel2-null(+/p) mice.Magel2-null mothers, fathers and virgin females demonstrated deficits in pup retrieval, nest building and pup-directed motivation, identifying a central role for this gene in parenting. Finally, we show thatMagel2-null mothers and fathers have a significant reduction in POA galanin expressing cells, which in tur...

Source: PLoS Genetics - October 19, 2023 Category: Genetics & Stem Cells Authors: Matthew J. Higgs Source Type: research