Shared and independent functions of aPKCλ and Par3 in skin tumorigenesis.

The polarity proteins Par3 and aPKC are key regulators of processes altered in cancer. Par3/aPKC are thought to dynamically interact with Par6 but increasing evidence suggests that aPKC and Par3 also exert complex-independent functions. Whereas aPKCλ serves as tumor promotor, Par3 can either promote or suppress tumorigenesis.

Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling.

Ceramides are crucial for skin barrier function, but little is known about the regulation of epidermal appendages and whether stem cell populations that control their regeneration depend on specific ceramide species. Here we demonstrate that ceramide synthase 4 (CerS4) is highly expressed in the epidermis of adult mice where it is localized in the interfollicular epidermis and defined populations within the pilosebaceous unit. Inactivation of CerS4 in mice resulted in precocious activation of hair follicle bulge stem cells while expanding the Lrig1(+) junctional zone and sebaceous glands.

Epidermal polarity genes in health and disease.

The epidermis of the skin is a highly polarized, metabolic tissue with important innate immune functions. The polarity of the epidermis is, for example, reflected in controlled changes in cell shape that accompany differentiation, oriented cell division, and the planar orientation of hair follicles and cilia. The establishment and maintenance of polarity is organized by a diverse set of polarity proteins that include transmembrane adhesion proteins, cytoskeletal scaffold proteins, and kinases.

Mammalian aPKC/Par polarity complex mediated regulation of epithelial division orientation and cell fate.

Oriented cell division is a key regulator of tissue architecture and crucial for morphogenesis and homeostasis. Balanced regulation of proliferation and differentiation is an essential property of tissues not only to drive morphogenesis but also to maintain and restore homeostasis. In many tissues orientation of cell division is coupled to the regulation of differentiation producing daughters with similar (symmetric cell division, SCD) or differential fate (asymmetric cell division, ACD).

aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation.

The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue.

Development of a three-dimensional in vitro model for longitudinal observation of cell behavior: monitoring by magnetic resonance imaging and optical imaging.

Purpose: The aim of this study is the development of a three-dimensional multicellular spheroid cell culture model for the longitudinal comparative and large-scale screening of cancer cell proliferation with noninvasive molecular imaging techniques under controlled and quantifiable conditions.

Procedures: The human glioblastoma cell line Gli36DeltaEGFR was genetically modified to constitutively express the fluorescence protein mCherry, and additionally labeled with iron oxide nanoparticles for high-field MRI detection. The proliferation of aggregates was longitudinally monitored with fluorescence imaging and correlated with aggregate size by light microscopy, while MRI measurements served localization in 3D space.