Numerous cadherin proteins, including N‐cadherin (Ncad), E‐cadherin (Ecad), Cadherin‐11 (Cad11) and Cadherin‐7 (Cad7), are expressed in the developing neural plate as well as in neural crest cells as they delaminate from the newly closed neural tube. To clarify whether these proteins function
independently or coordinately during development, we examined their relative expression in the cranial region of chick embryos. The results revealed surprising overlap of Ecad, Ncad and Cad7 in the neural tube, suggesting possible heterotypic interactions. Using a proximity ligation assay and co‐immunoprecipitation to test this hypothesis, we found that Ncad formed heterophilic complexes in the developing neural tube with Ecad. We also determined that modulation of either Ncad or Ecad levels led to reciprocal gain or reduction of the other cadherin protein. Altering levels of the two cadherin proteins affected the early fate specification of ectodermal derivatives, forcing an
aberrant choice between neural crest and epidermal cells. Finally, we identified that the availability of β‐catenin plays a critical role in maintaining the balance between Ncad and Ecad in early development since co‐expression of activated β‐catenin rescues the Ncad‐overexpression
phenotype. These results suggest that β‐catenin‐mediated balance of Ncad and Ecad proteins is critical for the normal development of the three ectodermal derivatives
