Chick cranial neural crest cells migrate by progressively refining the polarity of their protrusions

Summary In vivo quantitative imaging reveals that chick cranial neural crest cells throughout the migratory stream are morphologically polarized and migrate by progressively refining the polarity of their protrusions. Abstract To move directionally, cells can bias the generation of protrusions or select among randomly generated protrusions. Here we use 3D two-photon imaging of chick branchial arch 2 directed neural crest cells to probe how these mechanisms contribute to directed movement, whether a subset or the majority of cells polarize during movement, and how the different classes of protrusions relate to one another. We find that cells throughout the stream are morphologically polarized along the direction of overall stream movement and that there is a progressive sharpening of the morphological polarity program. Neural crest cells have weak spatial biases in filopodia generation and lifetime. Local bursts of filopodial generation precede the generation of larger protrusions. These larger protrusions are more spatially biased than the filopodia, and the subset of protrusions that power motility are the most polarized of all. Orientation rather than position is the best correlate of the protrusions that are selected for cell movement. This progressive polarity refinement strategy may enable neural crest cells to efficiently explore their environment and migrate accurately in the face of noisy guidance cues.