GLUCOSE-TRANSPORTER GLUT3 - ONTOGENY, TARGETING, AND ROLE IN THE MOUSE BLASTOCYST

The first differentiative event in mammalian development is segregatio n of the inner cell mass and trophectoderm (TE) lineages. The epitheli al TE cells pump fluid into the spherical blastocyst to form the blast ocyst cavity. This activity is fuelled by glucose supplied through fac ilitative glucose transporters. However, the reported kinetic characte ristics of blastocyst glucose transport are inconsistent with those of the previously identified transporters and suggested the presence of a high-affinity glucose carrier. We identified and localized the prima ry transporter in TE cells. It is glucose transporter GLUT3, previousl y described in the mouse as neuron-specific. In the differentiating em bryo, GLUT3 is targeted to the apical membranes of the polarized cells of the compacted morula and then to the apical membranes of TE cells where it has access to maternal glucose. In contrast, GLUT1 was restri cted to basolateral membranes of the outer TE cells in both compacted morulae and blastocysts. Using antisense oligodeoxynucleotides to spec ifically block protein expression, we confirmed that GLUT3 and not GLU T1 is the functional transporter for maternal glucose on the apical TE . More importantly, however, GLUT3 expression is required for blastocy st formation and hence this primary differentiation in mammalian devel opment. This requirement is independent of its function as a glucose t ransporter because blastocysts will form in the absence of glucose. Th us the vectorial expression of GLUT3 into the apical membrane domains of the outer cells of the morula, which in turn form the TE cells of t he blastocyst, is required for blastocyst formation.