AJP - Regu Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Regul Integr Comp Physiol (April 30, 2008). doi:10.1152/ajpregu.00182.2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Table
Right arrow All Versions of this Article:
295/1/R189    most recent
00182.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lui, J. C
Right arrow Articles by Baron, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lui, J. C
Right arrow Articles by Baron, J.
Submitted on March 11, 2008
Accepted on April 29, 2008

An Imprinted Gene Network that Controls Mammalian Somatic Growth is Down-Regulated During Postnatal Growth Deceleration in Multiple Organs

Julian C Lui1, Gabriela P. Finkielstain1, Kevin M. Barnes1, and Jeffrey Baron1*

1 DEB, NICHD, Bethesda, Maryland, United States

* To whom correspondence should be addressed. E-mail: jeffrey.baron{at}nih.gov.

In mammals, somatic growth is rapid in early postnatal life but decelerates with age and eventually halts, thus determining the adult body size of the species. This growth deceleration, which reflects declining proliferation, occurs simultaneously in multiple organs yet appears not to be coordinated by a systemic mechanism. We therefore hypothesized that growth deceleration results from a growth-limiting genetic program that is common to multiple tissues. Here, we identified a set of 11 imprinted genes that show down-regulation of mRNA expression with age in multiple organs. For these genes, Igf2, H19, Plagl1, Mest, Peg3, Dlk1, Gtl2, Grb10, Ndn, Cdkn1c, and SLC38a4, the declines show a temporal pattern similar to the decline in growth rate. All 11 genes have been implicated in the control of cell proliferation or somatic growth. Thus, our findings suggest that the declining expression of these genes contributes to coordinate growth deceleration in multiple tissues. We next hypothesized that the coordinate decline in expression of these imprinted genes is caused by altered methylation and consequent silencing of the expressed allele. Contrary to this hypothesis, the methylation status of the promoter regions of Mest, Peg3 and Plagl1 did not change with age. In summary, our findings suggest that a set of growth-regulating imprinted genes is expressed at high levels in multiple tissues in early postnatal life, contributing to rapid somatic growth, but that these genes are subsequently down-regulated in multiple tissues simultaneously, contributing to coordinate growth deceleration and cessation, thus imposing a fundamental limit on adult body size.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.