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. 2012 Oct;21(10):798-801.
doi: 10.1111/j.1600-0625.2012.01573.x. Epub 2012 Aug 7.

Tight Junction Properties Change During Epidermis Development

Free PMC article

Tight Junction Properties Change During Epidermis Development

Anna Celli et al. Exp Dermatol. .
Free PMC article


In terrestrial animals, the epidermal barrier transitions from covering an organism suspended in a liquid environment in utero, to protecting a terrestrial animal postnatally from air and environmental exposure. Tight junctions (TJ) are essential for establishing the epidermal permeability barrier during embryonic development and modulate normal epidermal development and barrier functions postnatally. We now report that TJ function, as well as claudin-1 and occludin expression, change in parallel during late epidermal development. Specifically, TJ block the paracellular movement of Lanthanum (La(3+)) early in rat in vivo prenatal epidermal development, at gestational days 18-19, with concurrent upregulation of claudin-1 and occludin. TJ then become more permeable to ions and water as the fetus approaches parturition, concomitant with development of the lipid epidermal permeability barrier, at days 20-21. This sequence is recapitulated in cultured human epidermal equivalents (HEE), as assessed both by ultrastructural studies comparing permeation of large and small molecules and by the standard electrophysiologic parameter of resistance (R), suggesting further that this pattern of development is intrinsic to mammalian epidermal development. These findings demonstrate that the role of TJ changes during epidermal development, and further suggest that the TJ-based and lipid-based epidermal permeability barriers are interdependent.


Figure 1
Figure 1. Tight Junction Formation in in Vivo Rat Fetal Development
A) Tight Junction protein expression in epidermis during the perinatal period. Western blots demonstrate that both claudin-1 and occludin expression peak at gestational day 18/19 and diminish as the fetal rat barrier is formed (day 20) and approaches parturition (day 22). Claudin-1 then peaks postnatally (PN), while occludin remains low. B) La3+ permeation at fetal day 18. La3+ permeates the viable epidermis until its diffusion is blocked by TJ between the lateral borders of the SG cells (arrow). C) La3+ permeation at postnatal day 3. In contrast to panel B, La3+ permeates through the lateral borders of the SG (arrows) and is blocked not at the SG, but instead is blocked at the SG/SC interface. SC= Stratum Corneum. SG= Stratum Granulosum. N=2–3 pups. Scale bar = 1 μm
Figure 2
Figure 2. Transepithelial Resistence measurements in Developing HEE
TER was measured in HEE cultured with those analyzed in SI Figure 1. An initial maximum is recorded at day 7. TER then drops until day 9, and increases again until day 11. n= 9–36 for each time point. Data are presented as the mean +/− SD.

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