Mechanisms, mechanics and function of epithelial–mesenchymal transitions in early development

Abstract

Epithelial-mesenchymal transitions (EMTs) are an important mechanism for reorganizing germ layers and tissues during embryonic development. They have both a morphogenic function in shaping the embryo and a patterning function in bringing about new juxtapositions of tissues, which allow further inductive patterning events to occur [Genesis 28 (2000) 23]. Whereas the mechanics of EMT in cultured cells is relatively well understood [reviewed in Biochem. Pharmacol. 60 (2000) 1091; Cell 105 (2001) 425; Bioessays 23 (2001) 912], surprisingly little is known about EMTs during embryonic development [reviewed in Acta Anat. 154 (1995) 8], and nowhere is the entire process well characterized within a single species. Embryonic (developmental) EMTs have properties that are not seen or are not obvious in culture systems or cancer cells. Developmental EMTs are part of a specific differentiative path and occur at a particular time and place. In some types of embryos, a relatively intact epithelium must be maintained while some of its cells de-epithelialize during EMT. In most cases de-epithelialization (loss of apical junctions) must occur in an orderly, patterned fashion in order that the proper morphogenesis results. Interestingly, we find that de-epithelialization is not always necessarily tightly coupled to the expression of mesenchymal phenotypes.Developmental EMTs are multi-step processes, though the interdependence and obligate order of the steps is not clear. The particulars of the process vary between tissues, species, and specific embryonic context. We will focus on 'primary' developmental EMTs, which are those occurring in the initial epiblast or embryonic epithelium. 'Secondary' developmental EMT events are those occurring in epithelial tissues that have reassembled within the embryo from mesenchymal cells. We will review and compare a number of primary EMT events from across the metazoans, and point out some of the many open questions that remain in this field.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…Moreover, studies in cultured mouse epithelia show that repression of occludin and claudins (claudin-3, claudin-4 and claudin-7) is performed by the direct interaction of Snail1 (Ikenouchi, 2003), what indicates that similar mechanism might be involved in the EMT of NC cells. Disassembly of tight junctions has been recognized as a transition into the gap junctions both in avian and amphibian EMT during early embryonic development (Shook and Keller, 2003). As a support for this observation an excess of the gap junction protein connexin-43α1 (Cx43α1) has been shown to significantly increase the migration rate of mouse cardiac NC cells.…”

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

“…The EMT process is a fundamental stage of embryogenesis (Mani et al, 2008;Morel et al, 2008). It also plays critical role in fibrosis (Kalluri et al, 2003) and cancer (Thiery et al, 2002;Shook et al, 2003;Kalluri et al, 2009;Thiery et al 2009). During EMT, epithelial cells break cell-cell and cell-matrix connections and migrate elsewhere (Radisky et al, 2008).…”

Basolateral junctions are sufficient to suppress epithelial invasion during Drosophila oogenesis

“…The junctional complexes consist of transmembrane receptors bound to cytoplasmic scaffolding proteins that link the complex to the cortical cytoskeleton (Knust, 2002). Epithelial cells can transform into migratory cells during embryonic morphogenesis, tissue repair, and regeneration, as well as numerous pathological conditions including cancer (Shook and Keller, 2003;Larue and Bellacosa, 2005;Thiery and Sleeman, 2006). These transitions correlate with extensive remodeling of cellular junctions (Grunert et al, 2003).…”