Formation and function of the periderm

University Of Iowa, Iowa City IA

Investigators

Abstract

The skin is the largest organ in the body and the skin barrier – provided by the epidermis – is critical for life of all vertebrates. Physically, the skin protects from external threats including infectious agents and prevents from excessive loss of water from the body. This barrier function is first provided during embryonic development by a transient protective layer called the periderm. Although the genesis and loss of the periderm are the first and last steps in the development of the epidermis, the precise role of this transient embryonic layer remain mysterious. To improve the dissemination of knowledge about embryology and epidermal barrier, there is a need to understand how the periderm is formed, what it does, and a need to teach about it in the classroom. This project will use advanced microscopy to get detailed information about the structure of the periderm. This study will engage scientific illustrators to depict the genesis and loss of the periderm in a public-accessible manner and promote its inclusion in textbooks. It will also involve high school students in observing developing skin under the microscope and teach them about the periderm. Students will sketch and annotate specimens seen under the microscope and create an artistic rendering of the same specimen, both of which will be exhibited for public viewing. The work train students from high school through graduate levels in original scientific research. To understand how the periderm contributes to epidermal fate and function, this project will utilize a mouse model system, the Irf6-deficient embryo. Interferon Regulatory Factor 6 (IRF6) has long been described as a master regulator of terminal epidermal differentiation. While analyzing Irf6-deficient embryos, it was observed the presence of adhesion-associated defects in the formation of the palate and the limbs, as well as differentiation-associated defects in the morphogenesis of epithelial cells in the epidermis (i.e., keratinocytes). These mutant embryos also exhibited significant thickening of the embryonic epidermis, with aberrant periderm differentiation and striking expansion of the suprabasal (i.e., spinous) compartment and lack of the uppermost epidermal layers (granular and cornified). These defects are associated with taut skin and a leaky epidermis, features that are incompatible with life. Together these data support the central hypothesis that peridermal cells are required for terminal differentiation of the epidermis, and that their development and fate are regulated by the transcription factor IRF6. The proposed study will test this hypothesis, utilizing a combination of classic ultrastructural microscopy, state-of-the art microscopy, quantitative image analysis, murine genetics (using specific alleles), and systematic experimental approaches. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.