The cellular basis of tissue separation

Abstract

The subdivision of the embryo into physically distinct regions is one of the most fundamental processes in development. General hypotheses for tissue separation based on differential adhesion or tension have been proposed in the past, but with little experimental support. During the last decade, the field has experienced a strong revival, largely driven by renewed interest in biophysical modeling of development. Here, I will discuss the various models of boundary formation and summarize recent studies that have shifted our understanding of the process from the simple juxtaposition of global tissue properties to the characterization of local cellular reactions. Current evidence favors a model whereby separation is controlled by cell surface cues, which, upon cell-cell contact, generate acute changes in cytoskeletal and adhesive properties to inhibit cell mixing, and whereby the integration of multiple local cues may dictate both the global morphogenetic properties of a tissue and its separation from adjacent cell populations.

Modulation of junction tension by tumor-suppressors and proto-oncogenes regulates cell-cell contacts

“…The segregation of tissues or of tissue compartments plays fundamental roles in the regulation of growth, patterning and morphogenesis (for a review, see Fagotto, 2014). Numerous tumor suppressors and proto-oncogenes share the common feature of promoting cell segregation apparent by the rounding of somatic clones upon their loss or gain of functions, respectively (Adler et al, 1998;Johnston et al, 1999;Edgar, 2000, 2002;Garoia et al, 2000;Baena-Lopez et al, 2005;Mao et al, 2006Mao et al, , 2011Worley et al, 2013).…”

Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis

“…Moreover, the extent to which sorting takes part in embryogenesis, not only to actuate cell motion but also to potentially aid differentiation and cell fate specification, is largely unknown (Fagotto, 2014).…”

Cell adhesion strength from cortical tension – an integration of concepts

“…The separation of two cell populations can be viewed as being based on low adhesion across the boundary, but increased actomyosin density and cytoskeletal tension at the boundary have also been implicated, for example at compartment boundaries in Drosophila (Dahmann et al, 2011;Fagotto, 2014). The concept of adhesion strength presents both mechanisms as two aspects of the same process -cortical tension increases at the boundary as adhesion is reduced, and vice versa.…”