Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup.
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 ident...
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2014
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oai:doaj.org-article:3f393f133352438498efee9639902e4d2021-11-18T05:37:34ZDevelopmental programming mediated by complementary roles of imprinted Grb10 in mother and pup.1544-91731545-788510.1371/journal.pbio.1001799https://doaj.org/article/3f393f133352438498efee9639902e4d2014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586114/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Developmental 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.Michael CowleyMichael CowleyAlastair S GarfieldMarta Madon-SimonMarika CharalambousRichard W ClarksonMatthew J SmalleyHoward KendrickAnthony R IslesAled J ParrySara CarneyRebecca J OakeyLora K HeislerKim MoorwoodJason B WolfAndrew WardPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 12, Iss 2, p e1001799 (2014) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Michael Cowley 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 Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| description |
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. |
| format |
article |
| author |
Michael Cowley 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 |
| author_facet |
Michael Cowley 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 |
| author_sort |
Michael Cowley |
| title |
Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| title_short |
Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| title_full |
Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| title_fullStr |
Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| title_full_unstemmed |
Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. |
| title_sort |
developmental programming mediated by complementary roles of imprinted grb10 in mother and pup. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/3f393f133352438498efee9639902e4d |
| work_keys_str_mv |
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