Neural crest cells must migrate long distances from the dorsal neural tube to their final destinations. How do they navigate to specific, reproducible target locations?
AThey follow random walks and end up at their destinations by chance
BThey follow a combination of attractive cues (chemotactic signals from targets), repulsive cues (inhibitory signals that prevent wrong paths), permissive substrates (ECM tracks), and cell-cell interactions (contact inhibition of locomotion that maintains stream cohesion)
CThey are passively transported by blood flow to their destinations
DEach neural crest cell has a unique GPS-like mechanism encoded in its genome
Neural crest migration is guided by multiple, redundant cue systems. Chemotactic signals (SDF-1/CXCL12 from targets) attract cells forward. Repulsive molecules (ephrins, Slit/Robo, semaphorins) create 'no-go zones' that restrict migration to defined corridors. Permissive ECM molecules (fibronectin, laminin) provide migration tracks. Contact inhibition of locomotion (CIL) causes cells that touch each other to repolarize and move apart, maintaining stream flow rather than aggregation. This multi-cue guidance system ensures reproducible migration to the correct destinations despite the complexity of the tissue environment.
Question 2 True / False
In collective cell migration, only the leader cells at the front sense the directional cue; follower cells are passively dragged along.
TTrue
FFalse
Answer: False
While leader cells do have specialized roles (larger lamellipodia, enhanced chemosensing), collective migration involves active participation by all cells in the group. Follower cells are mechanically coupled to leaders through adherens junctions and transmit forces through the group via supracellular actin cables. Follower cells also sense guidance cues and can become leaders if the original leaders are ablated. The collective responds to guidance cues more accurately than individual cells (a phenomenon called 'collective sensing' or the 'many wrongs principle') because the group averages out individual cell sensing errors. Collective migration is an active, cooperative process, not passive following.
Question 3 Short Answer
Explain how contact inhibition of locomotion (CIL) contributes to directional migration of neural crest cell streams.
Think about your answer, then reveal below.
Model answer: When two migrating neural crest cells contact each other, they retract their protrusions at the contact site, repolarize away from the contact, and move in opposite directions. Within a migrating stream, this means cells at the leading edge have free space ahead (no contacts to inhibit them) and contacts behind (pushing them forward), while cells at the rear are constantly pushed forward by contacts from all sides. CIL thus converts random motility into directional, stream-like migration without requiring every cell to independently sense a long-range chemotactic gradient. The leading cells sense the gradient; CIL transmits this directionality through the entire stream.
CIL was first described by Abercrombie in the 1950s for fibroblasts and was rediscovered as a key driver of neural crest migration by Mayor and colleagues. It is mediated by Wnt/PCP signaling and N-cadherin at cell-cell contacts and represents an elegant mechanism for converting local cell-cell interactions into population-level directional movement.