Cell News 3/2013
10
Regulation of the cyto-architecture in
epithelial morphogenesis and homeostasis
Susanne Vorhagen, Frederik Tellkamp and Carien M. Niessen
Department of Dermatology, Center for Molecular Medicine Cologne, Cologne
Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne
Abstract
Intercellular adhesion and polarity are crucial determinants
of tissue morphogenesis and tissue architecture. They coup-
le intercellular communication to cell shape, fate, migration,
and orientation of cell division (Niessen et al., 2011; Nelson,
2003; Macara, 2004; Niessen and Gottardi, 2008). The goal of
the Niessen laboratory is to understand how regulation of the
cyto-architecture controls the formation and maintenance of
stratifying epithelia such as the skin epidermis and how inter-
ference with this regulation contributes to disease. Our labora-
tory asks how key regulators of cell architecture, the aPKC/Par
polarity complex, or upstream niche signals of this complex, e.g.
insulin/IGF-1 or classical cadherins (Tunngal et al., 2005; Seifert
et al., 2009; Farese and Sajan, 2010) balance epidermal barri-
er homeostasis, cell fate and oriented cell division and thereby
control growth, differentiation, and stem cell behavior. In this
focus we will concentrate on the role of the aPKC/Par complex
in the regulation of mammalian epidermal barrier function, cell
fate and homeostasis.
Polarity: a short introduction
Polarity is a fundamental property of cells and tissues and defined
as the unequal distribution of molecules (RNAs, lipids, proteins)
within a cell to produce asymmetry in structure and function
at the cellular, tissue and organismal level. Establishment and
maintenance of polarity is a critical determinant of cell and
tissue architecture crucial for the regulation of cell behavior
in tissue morphogenesis, differentiation and homeostasis (Iden
and Collard, 2008; Macara and Mili, 2008; Simons and Mlodzik,
2008; St Johnston and Ahringer, 2010).
Polarity is established on two levels: 1) on the cellular level re-
sulting in asymmetry in individual cells, e.g. apico-basolateral
polarity, asymmetric cell division and the leading and trailing
edge of migrating cells. 2) on the tissue level, in which sub-
cellular structures and/or cells are aligned in the plane of the
tissue. This is also known as planar cell polarity (PCP). Examples
of tissue polarity are convergent extension movements, in which
cells rearrange their cytoskeleton in the plane of tissue to drive
directional intercalation of cells or the orientation of cilia, sig-
nal sensing cell organelles within a tissue seen e.g. in the kidney
or in the skin.
A core set of polarity proteins that are highly conserved throug-
hout Metazoa establish and maintain cell polarity or tissue
polarity. These basic signal pathways that cover either cell or
PCP pathways integrate to coordinate individual cell shape with
tissue architecture (Simons and Mlodzik, 2008). In addition, po-
larity signals also regulate and interact with other key determi-
nants of cell shape and tissue architecture, such as cytoskeletal
components, membrane trafficking, and adhesive junctions (Li
and Bowerman, 2010).
Initially mostly studied in lower organisms or in epithelial cell
culture systems, it is now clear that polarization is also a fun-
damental requirement for the proper functioning of mamma-
lian tissues (McCaffrey and Macara, 2009) and alterations in
the establishment and/or maintenance of asymmetry results
in a variety of human disease, such as kidney disease, hearing
dysfunction, inflammatory diseases and cancer (Huang and
Muthuswamy, 2010).
Polarity in stratifying epithelium:
the epidermis as an example
The epidermis of the skin is a stratifying multi-layered epithe-
lium that forms a barrier against external challenges and wa-
ter loss (Fig.1B). It consists of the interfollicular epidermis (IFE)
and epidermal appendages: hair follicles, sebaceous and sweat
glands. In the proliferating basal layer, epidermal keratinocytes
balance life long self-renewal with a spatiotemporally strictly
regulated terminal differentiation program necessary to form
the stratum corneum, a dead, cornified and water impermeable
cell layer (Candi et al., 2005; Koster, 2009). Different populati-
ons of stem and progenitor cells located in the basal layer of
the IFE and in specific areas of hair follicles guarantee constant
self-renewal under steady state conditions. In case of injury,
these progenitors also provide sufficient plasticity for the fast
replacement of lost tissue e.g upon wounding (Blanpain and
Fuchs, 2009; Watt and Jensen, 2009).
Many features within the epidermis are polarized and, more
importantly, this polarization is crucial for the formation and
function of the IFE and its appendages. During stratification ba-
sal keratinocytes differentiate, move suprabasally while under-
going controlled polarized cell shape changes until they reach
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