Thistransmembrane protein is responsible for theinflux ofzinc,manganese,iron, andcadmium.[8] ZIP8 is distributed among theembryo,placenta, andyolk sac during development.[9] Within the embryo, the concentration of ZIP8 is highest during the developmental period of different organ systems, specifically the heart where is it localized in theendothelial cells.Cardiac development is a zinc-dependent event. Beginning around mouse E8.0, the heart is in a tubular form with an outermyocardium layer and an innerendocardium layer, separated by cardiac jelly.[10] As development continues, trabeculation, theprotrusion ofcardiomyocytes into the cardiac jelly, begins and facilitates nutrient and oxygen exchange prior to the establishment ofcoronary vessels. Simultaneous with coronary circulation development, thetrabeculae then collapse into the ventricular wall in a process known ascompaction.Cardiomyocyte differentiation,proliferation, and trabeculae patterning is regulated throughNotch 1signaling, which is upregulated by the ECM.ADAMTS1,5,7, 15, and 19 are zincmetalloenzymes responsible for degrading the ECM prior to compaction.[11] Many studies have analyzed the effects of Slc39a8-/- on fetal heart development and have shown a decrease inzinc influx leading to an increase incardiomyocyte proliferation throughBMP10, hypertrabeculation through the upregulation of Notch1, and ventricular non-compaction due to the persistence of the ECM.
