Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

Abstract

Background: During embryonic development, cadherin switches are correlated with tissue remodelings, such as epithelium-to-mesenchyme transition (EMT). An E-to N-cadherin switch also occurs during neurogenesis, but this is not accompanied with EMT. The biological significance of this switch is currently unknown. Results: We analyzed the timing and kinetics of the E-to N-cadherin switch during early neural induction and neurulation in the chick embryo, in relation to the patterns of their transcriptional regulators. We found that deployment of the E-to N-cadherin switch program varies considerably along the embryonic axis. Rostrally in regions of primary neurulation, it occurs progressively both in time and space in a manner that appears neither in connection with morphological transformation of neural epithelial cells nor in synchrony with movements of neurulation. Caudally, in regions of secondary neurulation, neurogenesis was not associated with cadherin switch as N-cadherin pre-existed before formation of the neural tube. We also found that, during neural development, cadherin switch is orchestrated by a set of transcriptional regulators distinct from those involved in EMT. Conclusions: Our results indicate that cadherin switch correlates with the partition of the neurectoderm into its three main populations: ectoderm, neural crest, and neural tube.

The neural crest

“…A global switch from E-cadherin (cadherin 1) to N-cadherin (cadherin 2) expression occurs at the time of neural induction (Dady et al, 2012;Nandadasa et al, 2009) and thus neural plate and all pre-migratory NC cells express high levels of N-cadherin, with some residual levels of E-cadherin mostly found in the cephalic region. This is followed by another switch, from high to low N-cadherin expression, together with the de novo expression of weaker type II cadherins (6/7/11).…”

Tetraspanin18 is a FoxD3-responsive antagonist of cranial neural crest epithelial to mesenchymal transition that maintains Cadherin6B protein

“…Immunofluorescence was performed as previously described (Roffers-Agarwal et al, 2012) with the following antibodies: anti-HNK-1 (ATTC, Manassas, VA; 1:25), anti-Cad6B (DSHB, Iowa City, IA; clone CCD6B-1; 1:100 (Nakagawa and Takeichi, 1998)), anti-laminin (DSHB clone 31 or 31-2; 1:50), anti-Cad7 (DSHB clone CCD7-1; 1:50 (Nakagawa and Takeichi, 1998)), anti-N-cad (DSHB clone 6B3; 1:100), anti-E-cad (BD Transduction Laboratories; 1:250 (Dady et al, 2012)), anti-Snail2 (DSHB clone 62.1E6; 1:100), anti-b-catenin (Ctnnb1, BD Transduction Laboratories; 1:200 (Matson et al, 2011)) and anti-phosphohistone H3 (pH 3; Millipore; Billerica, MA; 1:250). Primary antibody was detected using donkey anti-mouse or donkey anti-rat secondary antibodies at 1:250 (Jackson Labs; West Grove, PA).…”

“…Cranial neural folds express cadherin-6B (Cad6B) and Ecadherin (E-cad), but not N-cadherin (N-cad). At cranial levels, Cad6B downregulation is necessary for neural crest EMT, while E-cad expression persists in migratory cells Dady et al, 2012;Nakagawa and Takeichi, 1995;Nakagawa and Takeichi, 1998). On the other hand, trunk neural crest cells express Cad6B and N-cad but not E-cad, and N-cad is lost during EMT but Cad6B persists during migration (Dady et al, 2012;Nakagawa and Takeichi, 1995;Park and Gumbiner, 2010;Shoval et al, 2007).…”

“…At cranial levels, Cad6B downregulation is necessary for neural crest EMT, while E-cad expression persists in migratory cells Dady et al, 2012;Nakagawa and Takeichi, 1995;Nakagawa and Takeichi, 1998). On the other hand, trunk neural crest cells express Cad6B and N-cad but not E-cad, and N-cad is lost during EMT but Cad6B persists during migration (Dady et al, 2012;Nakagawa and Takeichi, 1995;Park and Gumbiner, 2010;Shoval et al, 2007). Subsequently, the less adhesive, type II cadherin-7 (Cad7) is upregulated in migratory neural crest cells all along the axis (Chu et al, 2006;Nakagawa and Takeichi, 1995;Nakagawa and Takeichi, 1998).…”

Snail2 and Zeb2 repress P-cadherin to define embryonic territories in the chick embryo

“…All these data support the importance of E-cadherin repression in the definition of embryonic territories and subsequent tissue differentiation in the mouse. In the chick embryo, L-CAM was proposed to be the functional equivalent of E-cadherin in the mouse because it is expressed in the chick epiblast (Dady et al, 2012;Ohta et al, 2007). However, L-CAM is only faintly expressed in the epiblast of pre-primitive and primitive streak chick embryos (Moly et al, 2016 and this work).…”