Periderm prevents pathological epithelial adhesions during embryogenesis
Rebecca J. Richardson, … , Riitta Karikoski, Michael J. Dixon
Rebecca J. Richardson, … , Riitta Karikoski, Michael J. Dixon
Published August 18, 2014
Citation Information: J Clin Invest. 2014;124(9):3891-3900. https://doi.org/10.1172/JCI71946.
View: Text | PDF
Research Article Development

Periderm prevents pathological epithelial adhesions during embryogenesis

Abstract

Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer surface of the embryo late in development. Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm formation, resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus with cocoon syndrome, a lethal disorder that results from a nonsense mutation in IKKA, revealed an absence of periderm. Together, these data indicate that periderm plays a transient but fundamental role during embryogenesis by acting as a protective barrier that prevents pathological adhesion between immature, adhesion-competent epithelia. Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome.

Authors

Rebecca J. Richardson, Nigel L. Hammond, Pierre A. Coulombe, Carola Saloranta, Heidi O. Nousiainen, Riitta Salonen, Andrew Berry, Neil Hanley, Denis Headon, Riitta Karikoski, Michael J. Dixon

×

Figure 1

Periderm forms in a distinct pattern during embryogenesis.

Options: View larger image (or click on image) Download as PowerPoint
Periderm forms in a distinct pattern during embryogenesis. (A–D) E9 epid...
(A–D) E9 epidermis consists of a single layer of p63-positive, proliferative, cuboidal cells. (E–H) After E9, a single layer of keratin 17–positive, keratin 6–negative, proliferative, periderm cells (arrowheads) forms over the basal layer. (I–L) As further stratification of the epidermis proceeds and terminal differentiation commences; keratin 17– and keratin 6–positive periderm cells persist on the outermost surface (arrowheads). Proliferative periderm cells are still observed, but at a lower frequency than at earlier stages (L). (M–T) As terminal differentiation continues, keratin 17 expression is lost in the periderm, although it persists in developing hair follicles (N and R, asterisks). Keratin 6 persists as a marker of periderm at these later developmental stages (O and S). As the cornified layer forms, periderm detaches from the epidermal surface (arrowheads in Q and S). At later developmental stages, proliferation is restricted to the lower epidermal layers (P and T). (U–Y) Fluorescence visualization of [mK17 5′]-GFP transgenic mice reveals that periderm (green) forms in a distinct pattern during embryogenesis. Although absent at E9, periderm forms first over the developing tail and forelimb buds before spreading in a wave over the trunk and onto the head such that the embryo is covered in periderm by E14. Embryos were counterstained with propidium iodide (red). Dotted lines indicate the position of the basement membrane. Scale bars: 25 μm.