Cdon promotes neural crest migration by regulating N-cadherin localization

Abstract

Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.

Cadherins function during the collective cell migration of Xenopus Cranial Neural Crest cells: revisiting the role of E-cadherin

“…This behavior could be correlated with a robust expression of the N-cadherin (Dady et al, 2012; Duband et al, 1988; Lee et al, 2013; Nieto et al, 2016; Scarpa et al, 2015; Theveneau et al, 2010; Theveneau and Mayor, 2013). In other species, the expression of N-cadherin in the NC has also been observed (Duband et al, 1988; Monier-Gavelle and Duband, 1995; Piloto and Schilling, 2010; Powell et al, 2015; Xu et al, 2001). The cadherin switch seen during EMT events such as cancer metastasis, can be described to happen in either two ways.…”

“…1B). These events imply dynamic subcellular locali-zation of N-cadherin and the molecular underpinings of this dynamic are currently under investigation (Hardy et al, 2011; Powell et al, 2015). …”

Should I stay or should I go? Cadherin function and regulation in the neural crest

“…Cell-adhesion molecule-related/downstream by oncogenes (Cdon) also regulates N-cadherin levels in the zebrafish neural crest (Powell et al, 2015). Cdon is expressed in premigratory neural crest cells and at the beginning of migration in both the head and trunk but is absent from fully migratory crestin -positive neural crest cells.…”

Resolving in vivo gene expression during collective cell migration using an integrated RNAscope, immunohistochemistry and tissue clearing method

“…In vivo time-lapse imaging has revealed the dynamics of group cell behaviors in a number of embryo model organisms and included early gonad development (Irizarry and Stathopoulos, 2015; Paksa et al, 2016), gastrulation (Campinho et al, 2013; Omelchenko et al, 2014) hindgut formation (Nerurkar et al, 2017) and craniofacial patterning (Abbruzzese et al, 2016; Powell et al, 2015). However, our understanding of the molecular choreography underlying collective cell migration events has remained challenging due to difficulties with in vivo interrogation of gene and protein expression in neighboring cells and deep within the intact 3D embryo.…”