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1.
PLoS Genet ; 19(10): e1010961, 2023 10.
Article in English | MEDLINE | ID: mdl-37856383

ABSTRACT

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.


Subject(s)
Galanin , Parenting , Female , Animals , Mice , Galanin/genetics , Galanin/metabolism , Hypothalamus/metabolism , Genomic Imprinting/genetics , Phenotype , Antigens, Neoplasm/genetics , Proteins/genetics
2.
Nat Rev Genet ; 24(11): 783-796, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37714957

ABSTRACT

Genomic imprinting refers to the parent-of-origin expression of genes, which originates from epigenetic events in the mammalian germ line. The evolution of imprinting may reflect a conflict over resource allocation early in life, with silencing of paternal genes in offspring soliciting increased maternal provision and silencing of maternal genes limiting demands on the mother. Parental caregiving has been identified as an area of potential conflict, with several imprinted genes serendipitously found to directly influence the quality of maternal care. Recent systems biology approaches, based on single-cell RNA sequencing data, support a more deliberate relationship, which is reinforced by the finding that imprinted genes expressed in the offspring influence the quality of maternal caregiving. These bidirectional, reiterative relationships between parents and their offspring are critical both for short-term survival and for lifelong wellbeing, with clear implications for human health.


Subject(s)
Genomic Imprinting , Parenting , Animals , Humans , Gene Expression , Mammals/genetics
3.
R Soc Open Sci ; 7(2): 191162, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32257304

ABSTRACT

The animal purpose questionnaire (APQ) is a new instrument to measure human attitudes to animal use systematically across both species and purpose of use. This offers a more fine-grained approach to our understanding of how the belief in a specific animal's mental capacities relates to (dis-)agreement with their use for different human purposes. In the present study, 317 participants completed an online survey containing the APQ and the belief in animal mind (BAM) scale in a species-specific format, to test the prediction that levels of (dis-)agreement with animal use should mirror participants' judgements of animal sentience. The results obtained with the APQ confirmed that attitudes to animal use differed significantly across both purpose and species. Key findings included a relatively greater concern for dolphins and dogs over chimpanzees (suggesting that phylogenetic position is not the only determinant of attitudes to animal use). Across the purposes examined, respondents were largely negative about animal usage, with the exception that there was less disagreement if this was for medical research. Participants were also asked to provide demographic details such as gender and dietary preference. Regression analyses revealed high predictive power for species-specific BAM across five different kinds of animal use. General BAM scores, non-meat-eating and being female accounted for 31.5% of the total variability in APQ scores. The results indicate that BAM is a strong predictor of self-reported attitudes for using particular animals. However, the results showed some exceptions in the case of culturally typical 'produce' animals.

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