Abstract:
:The fetal genome regulates maternal physiology and behavior via its placenta, which produces hormones that act on the maternal hypothalamus. At the same time, the fetus itself develops a hypothalamus. In this study we show that many of the genes that regulate placental development also regulate the developing hypothalamus, and in mouse the coexpression of these genes is particularly high on embryonic days 12 and 13 (days E12-13). Such synchronized expression is regulated, in part, by the maternally imprinted gene, paternally expressed gene 3 (Peg3), which also is developmentally coexpressed in the hypothalamus and placenta at days E12-13. We further show that challenging this genomic linkage of hypothalamus and placenta with 24-h food deprivation results in disruption to coexpressed genes, primarily by affecting placental gene expression. Food deprivation also produces a significant decrease in Peg3 gene expression in the placenta, with consequences similar to many of the placental gene changes induced by Peg3 mutation. Such genomic dysregulation does not occur in the hypothalamus, where Peg3 expression increases with food deprivation. Thus, changes in gene expression brought about by food deprivation are consistent with the fetal genome's maintaining hypothalamic development at a cost to its placenta. This biased change to gene dysregulation in the placenta is linked to autophagy and ribosomal turnover, which sustain, in the short term, nutrient supply for the developing hypothalamus. Thus, the fetus controls its own destiny in times of acute starvation by short-term sacrifice of the placenta to preserve brain development.
journal_name
Proc Natl Acad Sci U S Aauthors
Broad KD,Keverne EBdoi
10.1073/pnas.1106022108subject
Has Abstractpub_date
2011-09-13 00:00:00pages
15237-41issue
37eissn
0027-8424issn
1091-6490pii
1106022108journal_volume
108pub_type
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