No description available.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thesis (D.Eng.)--Cleveland State University, 2008. / Abstract. Title from PDF t.p. (viewed on July 7, 2008). Includes bibliographical references (p. 150-176). Available online via the OhioLINK ETD Center. Also available in print.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 82-86.

Universiẗat, Diss., 2006--Würzburg.

Inaug.-diss.--Jena. / Lebenslauf. "Abdruck aus der Jenaischen zeitschrift für naturwissenschaft. Bd. XLV, n.f. XXXVIII, heft 2. 1909." "Literaturverzeichnis": p. 32-34.

Yes / During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57). Furthermore, the chromodomain- and SUMO E3 ligase-dependent Cbx4 activities differentially regulate proliferation, differentiation, and expression of nonepidermal genes in KCs. Finally, Cbx4 expression in KCs is directly regulated by p63 transcription factor, whereas Cbx4 overexpression is capable of partially rescuing the effects of p63 ablation on epidermal development. These data demonstrate that Cbx4 plays a crucial role in the p63-regulated program of epidermal differentiation, maintaining the epithelial identity and proliferative activity in KCs via repression of the selected nonepidermal lineage and cell cycle inhibitor genes.

No description available.

No description available.

Forming and maintaining an intact epidermal permeability barrier (EPB) is necessary to mammalian health and dysregulation of this process can result in serious complications. Tight junctions (TJs) and their integral proteins the Claudins (Cldns) have both structural and signaling importance to the skin barrier and the latter is most likely mediated via Cldn tail interaction with cytoplasmic proteins. Given that the family member Cldn6 is known to be important to EPB function, we set out to determine the contribution of its cytoplasmic tail domain to TJ-mediated homoeostasis. Using transgenic mouse models, we overexpressed epidermal-targeted tail truncation mutants and assessed EPB formation and maintenance. We then used yeast 2-hybrid and quantitative proteomic approaches to identify proteins that interact with this tail region and to assess the downstream effects of overexpressing these proteins in human keratinocytes in culture. We demonstrate that a 10 amino acid region in the cytoplasmic tail is required for efficient epidermal maturation and injury repair and that our mouse models may be applicable to postnatal epidermal maturation and human skin aging studies. We show that in addition to the known interacting partner ZO1, the C-terminal tail of Cldn6 also binds FIZ1 (Flt3 interacting zinc finger protein-1), which we characterize for the first time as a mitogenic factor for keratinocytes. FIZ1 stimulates autocrine pathways involving secreted heparin-binding factors IGFBP3 and DKK1, sensitization to IGF signaling, MAP/ERK activation and increased G1 progression. Specific transcription factors, protein kinases and signaling scaffolds that we identified as novel FIZ1-binding partners likely mediate this signaling. Our studies on the Cldn6 cytoplasmic tail support the importance of this region for epidermal maturation and for maintenance of skin homeostasis throughout life. They also delineate the potential for tail interactors such as ZO1 and FIZ1 to act in concert with Cldns in TJ-based signaling networks to regulate the balance between proliferation and differentiation in keratinocytes. These findings provide new insight into the role of the Cldn6 cytoplasmic tail and will ultimately aid in the development of new diagnostic tools and therapeutic approaches for the treatment of skin conditions rooted in barrier defects.