Neural crest cells bulldoze through the microenvironment using Aquaporin-1 to stabilize filopodia

Neural crest migration requires cells to move through an environment filled with dense extracellular matrix and mesoderm to reach targets throughout the vertebrate embryo. Here, we use high-resolution microscopy, computational modeling, and in vitro and in vivo cell invasion assays to investigate the function of Aquaporin-1 (AQP-1) signaling. We find that migrating lead cranial neural crest cells express AQP-1 mRNA and protein, implicating a biological role for water channel protein function during invasion. Differential AQP-1 levels affect neural crest cell speed, direction, as well as the length and stability of cell filopodia. Further, AQP-1 enhances matrix metalloprotease (MMP) activity and colocalizes with phosphorylated focal adhesion kinases (pFAK). Co-localization of AQP-1 with EphB guidance receptors in the same migrating neural crest cells raises novel implications for the concept of guided bulldozing by lead cells during migration.