The imprinted Phlda2 gene regulates extraembryonic energy stores.
An important difference between placental mammals and marsupials is the maturity of the fetus at birth. Placental mammals achieved this maturity by developing a complex and invasive placenta to support and prolong internal development. The exact genomic modifications that facilitated the evolution of this complex structure are unknown, but the emergence of genomic imprinting within mammalian lineages suggests a role for gene dosage. Here we show that a maximally altered placental structure is achieved by a single extra dose of the imprinted Phlda2 gene characterized by a dramatically reduced junctional zone and a decrease in stored glycogen. In addition, glycogen cells do not migrate into the maternal decidua in a timely fashion, but instead, Tpbpa-positive cells progressively mislocalize into the labyrinth. These defects are linked to a progressive restriction of embryonic growth from embryonic day 16.5. This work has identified a critical role for the imprinted Phlda2 gene in regulating glycogen storage in the eutherian placenta and implies that imprinting has provided a mechanism to boost nutrient supply to the fetus late in gestation, when the fetus is placing the highest demands on maternal resources, to enhance growth.
Tunster
S J
SJ
Genetics Division, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales CF10 3AX, United Kingdom.
Tycko
B
B
John
R M
RM
D000818:Animals; D020964:Embryo Loss; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D018392:Genomic Imprinting; D006003:Glycogen / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000502:physiology
D009687:Nuclear Proteins; C109277:TSSC3 protein; D006003:Glycogen