A zinc transporter gene required for development of the nervous system

Abstract

The essentiality of zinc for normal brain development is well established. It has been suggested that primary and secondary zinc deficiencies can contribute to the occurrence of numerous human birth defects, including many involving the central nervous system. In a recent study, we searched for zinc transporter genes that were critical for neurodevelopment. We confirmed that ZIP12 is a zinc transporter encoded by the gene slc39a12 that is highly expressed in the central nervous systems of human, mouse, and frog (Xenopus tropicalis).Using loss-of-function methods, we determined that ZIP12 is required for neuronal differentiation and neurite outgrowth and necessary for neurulation and embryonic viability. These results highlight an essential need for zinc regulation during embryogenesis and nervous system development. We suggest that slc39a12 is a candidate gene for inherited neurodevelopmental defects in humans.

Keywords: brain development; cell signaling; malnutrition; microtubules; neural tube defect; periconceptual nutrition; prenatal nutrition; prenatal vitamins; zinc deficiency; zinc supplementation.

Figure 1. Pathways by which ZIP12 and zinc transport may affect CREB activation and neuronal differentiation. Cell signaling pathways leading to CREB phosphorylation have been reviewed previously.