Orchestration of tissue‐scale mechanics and fate decisions by polarity signalling

Abstract

Eukaryotic development relies on dynamic cell shape changes and segregation of fate determinants to achieve coordinated compartmentalization at larger scale. Studies in invertebrates have identified polarity programmes essential for morphogenesis; however, less is known about their contribution to adult tissue maintenance. While polarity-dependent fate decisions in mammals utilize molecular machineries similar to invertebrates, the hierarchies and effectors can differ widely. Recent studies in epithelial systems disclosed an intriguing interplay of polarity proteins, adhesion molecules and mechanochemical pathways in tissue organization. Based on major advances in biophysics, genome editing, highresolution imaging and mathematical modelling, the cell polarity field has evolved to a remarkably multidisciplinary ground. Here, we review emerging concepts how polarity and cell fate are coupled, with emphasis on tissue-scale mechanisms, mechanobiology and mammalian models. Recent findings on the role of polarity signalling for tissue mechanics, micro-environmental functions and fate choices in health and disease will be summarized.

Role of mTOR Signaling Cascade in Epidermal Morphogenesis and Skin Barrier Formation

“…The epidermis is an excellent example of a polarized tissue. The polarity machinery, cellular adhesion and mechanical forces are coordinated to shape epidermal development and morphogenesis [ 133 ]. As mentioned, IGF-1/PI3K/mTORC2 signaling axis is crucial for epidermal stratification and barrier formation.…”

Lrig1- and Wnt-dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

“…Its outermost stratified epidermis is continuous with epidermal appendages like hair follicles and sweat glands (Chuong and Noveen, 1999). Proliferative, undifferentiated basal layer keratinocytes (KCs) attach to the underlying basement membrane and, following asymmetric cell division or delamination, progressively differentiate to constitute the spinous, granular and cornified layers (Blanpain and Fuchs, 2006;Dias Gomes and Iden, 2021;Gonzales and Fuchs, 2017;Ray and Lechler, 2011). The epidermis also hosts other resident cell types with crucial functions for the organism: neural-crest derived melanocytes (MCs) provide melanin for hair colorization and to protect KCs from ultraviolet (UV) damage (D'Orazio et al, 2013), whereas Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) constitute a first line of defense against environmental pathogens and malignant transformation in murine skin (Deckers et al, 2018;MacLeod et al, 2013).…”

Phase Separation in Cell Polarity

“…The three-dimensional shape of cells is often not uniform. Cells can polarize with asymmetrically distributed subcellular organelles or molecules along one or more axes, thus executing unique physiological functions. − For example, embryonic development and stem cell asymmetric division rely on the establishment of anterior-posterior or apical-basal polarity, respectively, to generate daughter cells with distinct fates; , the differences in morphology and structure between the apical and basal domains of epithelial cells ensure their exocrine, absorptive, and barrier functions . Extensive investigations on cell polarity reveal that the asymmetric clustering of certain proteins (e.g., the evolutionarily conserved Par3/Par6/aPKC complex) beneath local membrane regions is a common phenomenon and prerequisite for the establishment of polarity.…”