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

Autor: Higgs MJ; Behavioural Genetics Group, Centre for Neuropsychiatric, Genetics and Genomics, Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom., Webberley AE; Behavioural Genetics Group, Centre for Neuropsychiatric, Genetics and Genomics, Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom., Allan AJ; The Mary Lyon Centre, MRC Harwell, Didcot, United Kingdom., Talat M; The Mary Lyon Centre, MRC Harwell, Didcot, United Kingdom., John RM; School of Biosciences, Cardiff University, Cardiff, United Kingdom., Isles AR; Behavioural Genetics Group, Centre for Neuropsychiatric, Genetics and Genomics, Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2023 Oct 19; Vol. 19 (10), pp. e1010961. Date of Electronic Publication: 2023 Oct 19 (Print Publication: 2023).
DOI: 10.1371/journal.pgen.1010961
Abstrakt: 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 of Magel2 in the preoptic area galanin expressing neurons. We then examined the parenting behaviour of Magel2-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 that Magel2-null mothers and fathers have a significant reduction in POA galanin expressing cells, which in turn contributes to a reduced c-Fos response in the POA upon exposure to pups. Our findings identify a novel imprinted gene that impacts parenting behaviour and, moreover, demonstrates the utility of using single-cell RNA sequencing data to predict gene function from expression and in doing so here, have identified a purposeful role for genomic imprinting in mediating parental behaviour.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Higgs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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