Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation.

Abstract

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight-junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin-A chick-skin system is presented as a responsive model for the controlled study of junction assembly.The tight junction (zonula occludens) is a barrier to large molecule exchange between the lumina and intercellular spaces of epithelial tissues. Forming a continuous belt around the apices of polarized epithelia, it is visualized in thin section as a series of pentalaminar fusions between adjacent cells, and in freeze-fractured specimens as a network of fibrils or ridges and complementary furrows on the A and B faces, respectively (reviewed in references 23, 36, and 48). Whereas the distribution of this junction (16,19,43), its architecture (9,19,25,30), permeability properties (10,19,20), breakdown (48), and presumed mode of growth (37) have been described, a relatively simple laboratory model for inducing tight junctions in an epithelium normally deficient in such cellular components has been heretofore unavailable.The gap junction (nexus) is a highly ordered plasma membrane specialization considered essen-

Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier.

“…Moreover, our laboratory has shown that thyroid hormone also accelerates fetal epidermal barrier ontogenesis (8). Furthermore, vitamin A and its analogues exhibit profound effects on fetal epidermal development (36,37). Finally, recent studies have shown that overexpression of a mutated RAR␣ in fetal murine skin results in aberrant epidermal development (17,18).…”

Control of intercellular communication by voltage dependence of gap junctional conductance

“…Spray et al, 1981bSpray et al, , 1982a, relatively large changes in intracellular calcium ion (Spray et al, 1982b), or presumably by changes in the number of junctional channels (which can be under hormonal control; cf. Merk and McNutt, 1972;Elias and Friend, 1976). Changes in nonjunctional conductances also can affect coupling (cf.…”

The actions of retinoids on cellular growth correlate with their actions on gap junctional communication.

“…Further indicative here are electron-microscopic studies in tumor and skin tissues, showing that the gap-junction area increases after long term retinoic acid treatment (Prutkin, 1975;Elias and Friend, 1976;Elias et al, 1980). These studies provided no information on permeability, but in view of the present results it seems plausible that the enlarged gap-junction areas reflected increases in the number of (open) channels.…”