FORMATION OF THE EPIDERMAL CALCIUM GRADIENT COINCIDES WITH KEY MILESTONES OF BARRIER ONTOGENY IN THE RODENT

The epidermal permeability barrier forms late in gestation, coincident with decreased lipid synthesis, increased lipid processing, and devel opment of a mature, multilayered stratum corneum. Prior studies have s hown that changes in the epidermal Ca++ gradient in vivo regulate lame llar body secretion and lipid synthesis, and modulations in extracellu lar Ca++ in vitro also regulate keratinocyte differentiation. We asked here whether a Ca++ gradient forms in fetal epidermis in utero, and w hether its emergence correlates with key developmental milestones of b arrier formation and stratum corneum development. Using either ion pre cipitation or proton induced X-ray emission analysis of fetal mouse an d rat skin, we showed that a Ca++ gradient is not present at gestation al days 16-18, prior to barrier formation, and that a gradient forms c oincident with the emergence of barrier competence (day 19, mouse; day 20, rat) prior to birth, These results are consistent with a role for Ca++ in the regulation of key metabolic events leading to barrier for mation. Whether the calcium gradient is formed actively or passively r emains to be determined.