Chick cranial neural crest cells use progressive polarity refinement, not contact inhibition of locomotion, to guide their migration

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, in contrast to Xenopus, cells throughout the stream are morphologically polarized along the direction of overall stream movement and do not exhibit contact inhibition of locomotion. Instead chick neural crest cells display 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 are productive for motility are the most polarized of all. Orientation rather than position is the best correlate of the protrusions that are selected for cell guidance. 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.

Neural crest migration with continuous cell states

“…Contact-inhibition of locomotion has been studied as a mechanism enabling collective migration both in computational models and in Xenopus embryos [6], but this has not been observed in chick cranial neural crest [18]. Another alternative to contact guidance would be pulling of followers by leader cells [35], and vice versa, which would improve overall stream cohesion.…”

“…What has hitherto not been investigated is whether leader-follower cell states need be discrete, or could lie on a continuum. This question is relevant in light of ongoing debate in the literature about whether mechanisms of neural crest cell migration are common or distinct in different model organisms [16,17,18].…”

Neural crest delamination and migration: Looking forward to the next 150 years

“…Another study proposed that chick cephalic NC cells do not rely on contact-inhibition to perform directional migration. However, this work was solely based on descriptive data (Genuth, Allen, Mikawa, & Weiner, 2018). None of which is incompatible with the function of CIL at high cell density.…”

PDGF-A suppresses contact inhibition during directional collective cell migration

“…Suppression occurs in a polarized manner, which has the ultimate effect of orienting cells towards the animal pole, in the direction of overall LEM migration. Cell orientation based on the differential survival of lamellipodia has also been described for the chick neural crest (Genuth et al, 2018). Similar to LEM cells, chick neural crest cells do not exhibit contact inhibition of migration in situ, and a combination of increased formation and differential survival of protrusions pointing in the overall direction of movement effectively polarizes cells throughout the translocating cell stream.…”