[6][7] The discovery of cadherin cell-cell adhesion proteins is attributed to Masatoshi Takeichi, whose experience with adhering epithelial cells began in 1966.

His interest in cell adherence was sparked, and he moved on to examine attachment in other conditions such as in the presence of protein, magnesium, and calcium.

Using rats immunized with F9 cells, he worked with an undergraduate student in the Okada laboratory, Noboru Suzuki, to generate mouse antibodies called ECCD1.

[13] The delay Takeichi experienced in specifically discovering Ecadherin was most likely due to the model he used to initially investigate cell adherence.

The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail.

[15] E-cadherin (epithelial) is the most well-studied member of the cadherin family and is an essential transmembrane protein within adherens junctions.

[20] E-cadherin adhesions inhibit growth signals, which initiates a kinase cascade that excludes the transcription factor YAP from the nucleus.

Physiologically, branching is an important feature that allows tissues, such as salivary glands and pancreatic buds, to maximize functional surface areas.

[23][24] Single-layered branching occurs as nearby mechanical influences, such as airway smooth muscle cells, cause epithelial sheets buckle.

[25] Stratified epithelial cannot respond to stimulus in the same way due to the absence of internal space (i.e. lumen) that allows tissue sheet flexibility.

[27] While this gradient is important for cell sorting within the tissue layers, additional experiments show that the physical generation of buds is dependent on cell-matrix interactions[13].

Gastrulation is a fundamental phase of vertebrate development in which three primary germ layers are defined, ectoderm, mesoderm, and endoderm.

Cellular adhesion must still be considered for a complete understanding of progenitor sorting, as it directly  diminishes the energetic effects of tension.

[31] It is known that cells that begin to internalize at the dorsal surface of the embryo mobilize to extend the axis and direct posterior prechordal plate and notochord precursors.

[34] Knockdowns in leading and following cell groups both resulted in a loss of orientation, which could be rescued by re-expressing E-cadherin.

The intracellular domain of E-cadherin is essential due to its mechanotransduction characteristics; it interacts with alpha-catenin and vinculin and altogether allows for the mechanosensation of tension.

[35][36][37] The exact mechanism on how mechanosensation directs actin-rich protrusions is yet to be elucidated, however initial investigations suggest regulation of PI3K activity is involved.

[32] Adherens junctions (AJs) form homotypic dimers between neighboring cells, where the intracellular protein complex interacts with the actomyosin cytoskeleton.

p120-catenin controls E-cadherin membrane localization, while β-catenin and α-catenin provide the link that connect AJs to the cytoskeleton.

Rac1 and its effectors act at the front edge of this structure to initiate actin polymerization, allowing the cell to generate force at the cellular margin and forward movement.

[43] This tumour suppressor protein relocalizes from cortical cell-cell junctions to the cytoplasm during migration to coordinate Rac1 activation.

[44] CDH1 (gene) has been shown to interact with Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis.

[64] E-cadherin and N-cadherin temporal-spatial expression are tightly regulated during cranial suture fusion in craniofacial development.

Together with other mechanisms, such as constitutive RTK activation, E-cadherin loss can lead cancer cells to the mesenchymal state and undergo metastasis.