Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into first pharyngeal arch

Vertebrate cranial neural crest cells (CNCC) are multipotent. Proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. Here, we report that a novel {beta}-catenin-controlled switch in the cell arrangement is critical in patterning CNCC. In mouse embryos, at the first pharyngeal arch axial level, membrane {beta}-catenin levels correlate with the extent of cell-cell adhesion and thus, with a collective or a dispersed state of CNCC. Using in vitro human neural crest model and chemical modulators of {beta}-catenin levels, we show a requirement for down-modulating {beta}-catenin for the collective-to-dispersed switch. Similarly, in {beta}-catenin gain of function mutant mouse embryos, CNCC fail to disperse, which may underlie their failure to populate first pharyngeal arch. Thus, we show that {beta}-catenin-mediated regulation of CNCC tissue architecture, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.\n\nSummary statementThe report shows a crucial step in cranial neural crest patterning. Neural crest cells invading the pharyngeal arches transition from a collective to a dispersed state. This transition in cell arrangement is dependent on membrane {beta}-catenin levels.