Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup

Cowley, Michael, Garfield, Alastair S., Madon-Simon, Marta, Charalambous, Marika, Clarkson, Richard W. E. ORCID: https://orcid.org/0000-0001-7389-8673, Smalley, Matthew John ORCID: https://orcid.org/0000-0001-9540-1146, Kendrick, Howard, Isles, Anthony Roger ORCID: https://orcid.org/0000-0002-7587-5712, Parry, Aled J., Carney, Sara, Oakey, Rebecca J., Heisler, Lora K., Moorwood, Kim, Wolf, Jason B. and Ward, Andrew 2014. Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. PLoS Biology 12 (2) , e1001799. 10.1371/journal.pbio.1001799

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Abstract

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) European Cancer Stem Cell Research Institute (ECSCRI) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Public Library of Science
ISSN:	1545-7885
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	15 January 2014
Last Modified:	13 Dec 2023 07:26
URI:	https://orca.cardiff.ac.uk/id/eprint/62778

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