THE J OURNAL Of' I NVESTIGATIVE D ERM ATOLOGY , 65:7 ) - 84. ) 975 Vol. 65, No.) Copy right © 1975 by The Willia ms & Wilkins Co. Printed in U. S.A. THE EPIDERMAL- DERMAL JUNCTION ROBERT A. BRIGGA MAN , M .D ., AN D CLAYTON E. WH EELER. JR., M .D . Department of Dermatology, The University of N orth Carolina Schoo l of M edicine, Chapel H ill , North Carolina Ultrastructurally, the epiderma l- dermal junction is composed of four component areas: (1) the basal cell plasma membrane with its specialized attachment dev ices or hemidesmo­ somes, (2) an electron-lucent area, the lamina lucida, (3) the basal lamina, and (4) the sub-b asal lamina fibrous components, including anchoring fibrils, dermal microfibril bundles, and coll agen fibers. The light microscopic " basement membrane" comprises only the s ub-basal lamina fibrous zone. Other cell types, including melanocytes and M erkel cell s, are also found at the epidermal- dermal junction. Structures at the junction deri ve their origin from t he epidermis and dermis: the basal lamina is primarily of epidermal origin , t he anchoring fibrils of dermal origin . The junction serves t he following functions: (1) epidermal- dermal adherence, (2) mechanical support fo r the epidermis, and (3) a barrier to the exchange of cells and of some large molecules across the junction. The structures situated at the junction between ing fibers" (4], " pre-elastic fibers" [5 ], and "elas­ the epidermis and dermis constitute an anatomic tofibrils" [6], extend perpendicularl y toward the functional unit, the epidermal- dermal junction. interface . In co mbined PAS- orcein-stained speci­ The purpose of this paper is to review the current mens, these fibers pass into the PAS-pos itive information on its morphology, development, for­ basement membrane. They stain positively with mation, composition, and function. Selected path ­ elastic tissue stain but are more lig htly stained ologic alterations of the junction will be consid­ than the coarse elastic fibers of the reticul ar ered, particularly those which reveal information ,dermis. Silver (reticulum) stains reveal a zone of about its structure and function . The reader is fin e silver-positive fibers in the papillary dermis referred to several excellent earlier revi ews of this immediately under t he epidermis which is also su bject [1 - 3 ). referred to as t he light microscopic " basement membrane. " It corresponds to the P AS-positive STRUCT URE AT THE EPIDERMAL- DERMAL JUNCTION " basement membrane" in localization. By means Ligh t M icroscopy of immunoflu orescen t antibody techniques, immu­ prominent undulations of t he boundary zo ne noglobulins wi th specific localization to the base­ between t he epidermis and the dermis form the ment membrane zone can be found in t he serum dennal papillae- rete ridge pattern, whose specifi c and the skin lesions of patients with bullous fe at ures are characteristic of different regions of pemphigoid a nd the skin of patients wi th lupus t he skin surface. Special stains aid in the definition erythematosus [7]. of this zone by light mi croscopy (Fig. 1) . Periodic The prevailing view of the epidermal- dermal acid- Schiff stain demonstrates a thin, uniform, junction at the li ght microscopic level is t hat it is a nonfibriJIar area of intense staining at the feltwork of reticulum (silver-positive) fibers and epidermal- dermal interface which is sometimes probably elastic fibers embedded in a neutral called the light microscopic or PAS-posit ive "base­ glycoprotein (PAS-positive) matrix and containing ment membrane." In the papillary dermis, moder­ an tige nic materi als which in teract wi th " ba ement ately coarse elastic fibers (orcein stain) form a membrane" antibodies. felt work running roughly parallel to the in terface, Electron Microscopy but separated by a narrow distance. From this fe ltwork, fin e fibers, variously called "fin e connect- When viewed by electron mi croscopy [8- 10 ], a high level of structural organi zation which is not appreciated by light mi croscopy is seen at t he This study was supported by Research Grant 2 ROI epidermal- dermal junction. T his structure can be AM 10546 and Dermatology Training Grant 5 ROl AM divided in to four components: (1) basal cell plasma 05298 from the N ational Instit utes of H ealt h, a nd Grant RR 46 from the Genera l Clinical Resea rch Centers membrane with its special attachment devices, Branch of t he Division of Research Resources, U. S. hemidesmosomes, (2) t he lamina lucida (o r inter­ Public H ealth Service. membranous space), (3) the basal lamina (basal R eprint requests to: Dr. R. A. Briggama n, Depa rtment membrane, basement membrane, lamina densa, of D ermatology, School of M edicine, The Univers ity of North Carolina at Chapel Hill , Chapel Hill , North adepidermal membrane) , and (4) the sub-basal Carolina 27514. lamina fibrous elements composed of at least three 71 72 BRiGGAMAN AND WIiEELER Vol . 65, No. I the sub-basal dense plaque into the basal laminl\ (Figs. 7, 8). These filaments were first describecl by Kobayasi (10,19] and termed "anchoring fila. ments" [1 6,20]. Randomly oriented filaments resembling anchoring filaments can be seen in the lamina lucida away from hemidesmosom es, but PAS ELASTIC RETICULUM they are much less numerous in this latter location In the area of the epidermal- d erma l junctiol; FIG. 1. Period ic acid - Schiff (PAS), elastic, and reticu­ lum staining properties of the epidermal- dermal junction. where adjacent epidermal basal cells meet, the lamina lucida and the intercellular space between adjacent basal cells are contiguous even though different types: anchoring fibrils, bundles of fibrils resembling microfibrils, and sin gle collagen fibers some evid ence indicates that they have d ifferent (Figs. 2- 6). staining and permeability properties. Both ru. Basal cell plasma membrane-hemidesmosomes . the.nium ~ed [1 6] and pemphigus antibody [211 The dermal surface of the basal cell plasma mem ­ stam the Illtercellular space, but not the lamina brane is irregula rl y convoluted with interdigitating lucida. In addition, la nt hanum readily p e rme ate ~ cytoplas mic projections a nd derma l invaginations the intercellular space but not the lamina lucid ~ (Fig. 2); seldom is it nat for m ore than a short [22]. These dlfferences suggest that the two differ distance. These convolutions are not the same as in composition but what the differences are has not the dermal papill ae- rete undulations seen at the yet been determined. ligh t microscopic level. The plasma membra ne Basal lamina. The basal lamina is a continUOl! itself is approxim ately 7 to 9 nanometers (nm) electron-dense layer which has a granular amOr, thick and is composed of three asymmetrical phous appearance in Epon-embedded specimens layers: a thicker internal leaflet which abuts the but is fibrillar in Vestopal specimens. This m ay cytopl asm ; a n intermediate, more electron-lucent indicate a two-phase system, i.e., fibrillar compo. zone; and a relatively thin external leaflet (Figs. 7, nents e mbedded in an amorphous granular mate. 8). Pinocytotic vesicles occur frequently a long the ri a l. True breaks or gaps of the basal lamina are plasma membrane (Fig. 5) which is studded at comparatively rare in normal skin and must be intervals with electron-dense thickenings or he mi­ distinguished from areas of tangential section desmosomes (basal attachment plaques, basal which obscure the orderly laminated structures dense bodies) (Figs. 2-4). The ultrastructure of the described above. The basal lamina varies in thick, hemidesmosome has been examined repeatedly ness and density particularly beneath t he hemides, over the years [11- 17), the most recent studies mosomes where it is t hicker and more dense. Th ~ indicating that it is similar to but not identical reduplication of the basal lamina, which is com, with t he desmosome. An electron-opaque thicken­ m an in normal skin (Fig. 6), may result from th ~ ing, t he "attachment pl aque," approximately 20 to remodeling of the epidermal- dermal junction a 40 nm thick, is present on the cytoplasmic surface basal cells are released to migrate toward th ~ of the internal leaflet of the plasma membrane surface and from the subsequent re-formation of (Figs. 7, 8). On sections cut exactly perpendicular the basal lamina beneath another basal eel! which to the plasma membrane, tonofilaments radiate takes up residence at the same location. Since the toward the attachment plaque but actually termi­ basal la mina is a durable structure [23 ], the olq n ate in a relatively electron-dense area separated epidermal- d ermal junction, including the basal from the plaque by a narrow, relatively electron­ lamina, a nchoring fibrils, and other fibrillar ele, lucent zone. On obli que sections, the tonofilaments ments, m ay persist for some time after the forma. seem to fu se with the attachment plaque. The tion of a new junction. Partially destroyed basal external lean et of the plasma m embrane can be lamina can a lso be seen in some areas. Reduplica, seen on high resolution electron micrographs as a tion of the basal lamina is also seen beneath fine line (M line) on the outer surface of the attach­ melanocytes at the junction (Fig. 9). ment plaque [1 5,17 ]. Sub-basalla.mina fibrous elem ents. Three types Lamina lu cida . The lamina lucida or intermem­ of fibrous structures found beneath the basal branous space is a n electron-lucent zone which lamina will be discussed : (1) anchoring fibrils, (2) separates the plasma membrane from the basal microfibrils arranged in bundles, and (3) collagen lamina (Figs.