Abstract
Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, although its function in this tissue has been hitherto unclear. Disruption of the apoB gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoB-containing lipoproteins. The lack of apoB in the visceral endoderm resulted in an accumulation of intracellular lipid droplets, an absence of lipoproteins from the secretory pathway, and reduced concentrations of cholesterol and alpha-tocopherol in tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an intermediate phenotype. Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediated synthesis and secretion of apoB-containing lipoproteins.
Highlights
Apolipoprotein B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, its function in this tissue has been hitherto unclear
Because apoB deficiency results in embryonic lethality and because the temporal expression pattern of apoB mRNA in mouse development had not been studied previously, we investigated the temporal expression of apoB mRNA in mouse embryos using an RT-PCRassay (Fig. 1A)
Because our findings indicated that the lack of apoB in the yolk sac visceral endodermal cells was associated with impaired lipoprotein synthesis and a resultant defect in lipid export from these cells, we examined whether apoB deficiency was associated with reduced cholesterol or a-tocopherol concentrations in intraembryonic tissues of upoB+/+,upoB+/,and upoB-/-embryos (Fig. 6 ) .At 9.5-10.5 days of age, cholesterol concentrations were reduced in upoB+/- embryos
Summary
Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, its function in this tissue has been hitherto unclear. We demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoBcontaining lipoproteins. I Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediatedsynthesis and secretion of apokontaining lipoproteins.-Farese, R. -the yolk sac and its associated vitelline circulation serve as the primary interface between the embryo and maternal tissues and are thought to play a major nutritive role for the mouse embryo during the early gestational period, at least until a functioning chorioallantoic placenta is established (days 9-10). Whether apoB is expressed at earlier time points in development or whether apoB expression at these early time points is associated with the production of apoB-containing lipoproteins has not been investigated
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