The genetics of essential metal homeostasis during development

Abstract

The essential metals copper, zinc, and iron play key roles in embryonic, fetal, and postnatal development in higher eukaryotes. Recent advances in our understanding of the molecules involved in the intricate control of the homeostasis of these metals and the availability of natural mutations and targeted mutations in many of the genes involved have allowed for elucidation of the diverse roles of these metals during development. Evidence suggests that the ability of the embryo to control the homeostasis of these metals becomes essential at the blastocyst stage and during early morphogenesis. However, these metals play unique roles throughout development and exert pleiotropic, metal-specific, and often cell-specific effects on morphogenesis, growth, and differentiation. Herein, we briefly review the major players known to be involved in the homeostasis of each of these essential metals and their known roles in development.

Ovarian gene transcription and effect of cadmium pre-exposure during artificial sexual maturation of the European eel (Anguilla anguilla)

“…These maternal mRNAs are translated after fertilization to cope with the needs of embryogenesis (Spirin 1994;Vassalli and Stutz 1995;Stebbins-Boaz and Richter 1997). In the particular case of MTs, activation of mRNAs after fertilization could aim to cope with the needs of metalloproteins that store and donate essential metals, notably copper and zinc which are essential for embryogenesis (Kambe et al 2008). Interestingly, and this, at the opposite to control eels, the significant increase in mts transcripts observed at the end of the experiment was effectively marked by a concomitant and significant increase in ovarian MTs protein content of Cd pre-contaminated eels.…”

Does promoter methylation of the SLC30A5 (ZnT5) zinc transporter gene contribute to the ageing-related decline in zinc status?

“…Expression of other Zn transporters involved in dietary Zn absorption may also be potentially regulated by DNA methylation. ZnT1 is expressed in the intestinal mucosa, localised to the basolateral membrane of the enterocyte, and is involved in the transport of Zn from the enterocyte into the portal blood (27,51) . Since there is a CpG island within the promoter region of this gene (52) it is reasonable to speculate that ZnT1 expression, and subsequently transport of Zn into the portal blood, may be modified as a consequence of age-related changes in DNA methylation status.…”

An Overview of a Wide Range of Functions of ZnT and Zip Zinc Transporters in the Secretory Pathway

“…[16][17][18][19] They are classified into two families: zinc transporter (ZnT: vertebrate cation diffusion facilitator family proteins, Slc30a family) and Zip (Zrt/Irt-like protein, Slc39a family). [20][21][22] Most ZnT transporters are predicted to have six transmembrane domains (TMDs), while Zip transporters have eight TMDs.…”

“…16,19,22) Among vertebrates, some highly specialized cell types have cytoplasmic vesicles/granules accumulating high zinc contents. For example, pancreatic cells, 50) specialized glutamatergic neurons, 51) epithelial cells of the lateral prostate, 52) pigment epithelial cells in the retina, 53,54) granular convoluted tubule cells of submaxillary gland, 55) pituitary secretory cells, 56) sperm cells, 57,58) mast cells 59,60) and secreting mammary epithelial cells 61) are known to have zinccontaining vesicles/granules.…”