Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

Michael Cowley, Alastair S. Garfield, Marta Madon-Simon, Marika Charalambous, Richard W. Clarkson, Matthew J. Smalley, Howard Kendrick, Anthony R. Isles, Aled J. Parry, Sara Carney, Rebecca J. Oakey, Lora K. Heisler, Kim Moorwood, Jason B. Wolf, Andrew Ward (Corresponding Author)

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Article number1001799
JournalPLoS Biology
Volume12
Issue number2
DOIs
Publication statusPublished - 25 Feb 2014

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pups
health status
Health Status
Growth
Fats
Health
maternal nutrition
genomic imprinting
supply balance
postpartum period
Adiposity
adiposity
Nutrition
lipids
adulthood
Nutrients
homeostasis
Homeostasis
Genes
Mothers

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Cowley, M., Garfield, A. S., Madon-Simon, M., Charalambous, M., Clarkson, R. W., Smalley, M. J., ... Ward, A. (2014). Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup. PLoS Biology, 12(2), [1001799]. https://doi.org/10.1371/journal.pbio.1001799

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.; Smalley, Matthew J.; Kendrick, Howard; Isles, Anthony R.; Parry, Aled J.; Carney, Sara; Oakey, Rebecca J.; Heisler, Lora K.; Moorwood, Kim; Wolf, Jason B.; Ward, Andrew (Corresponding Author).

In: PLoS Biology, Vol. 12, No. 2, 1001799, 25.02.2014.

Research output: Contribution to journalArticle

Cowley, M, Garfield, AS, Madon-Simon, M, Charalambous, M, Clarkson, RW, Smalley, MJ, Kendrick, H, Isles, AR, Parry, AJ, Carney, S, Oakey, RJ, Heisler, LK, Moorwood, K, Wolf, JB & Ward, A 2014, 'Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup', PLoS Biology, vol. 12, no. 2, 1001799. https://doi.org/10.1371/journal.pbio.1001799
Cowley M, Garfield AS, Madon-Simon M, Charalambous M, Clarkson RW, Smalley MJ et al. Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup. PLoS Biology. 2014 Feb 25;12(2). 1001799. https://doi.org/10.1371/journal.pbio.1001799
Cowley, Michael ; Garfield, Alastair S. ; Madon-Simon, Marta ; Charalambous, Marika ; Clarkson, Richard W. ; Smalley, Matthew J. ; Kendrick, Howard ; Isles, Anthony R. ; Parry, Aled J. ; Carney, Sara ; Oakey, Rebecca J. ; Heisler, Lora K. ; Moorwood, Kim ; Wolf, Jason B. ; Ward, Andrew. / Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup. In: PLoS Biology. 2014 ; Vol. 12, No. 2.
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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.",
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