Figure 2. The three phases of cranial neural crest cell migration and characteristic cell behaviors. Phase 1: Acquisition of directed migration along the dorsolateral pathway.

(A) Cranial NCC migration starts around Hamburger and Hamilton (HH) Stage 11 in chick. During Phase I, the lead cranial NCCs emerge from the dorsal neural tube (beige). Initially the cranial NCCs do not exhibit directed orientation (orange NCCs), but within a short distance from the dorsal neural tube, they acquire directionality (yellow NCCs). (B) The cranial NCCs communicate with each other and the microenvironment, by touch. First, a NCC touches the ectoderm and receives direction information. Second, there is follow-the-leader behavior, where one NCC touches another, and then with or without filopodia retraction, follows the lead NCC. Phase II: Homing to the branchial arches. (C) After acquiring directionality, cranial NCCs migrate in a directed manner and exhibit a bipolar phenotype (green NCCs). Along the migratory route, cranial NCCs stop, retract filopodia and divide (red NCCs). As they invade the target site, the cranial NCCs extend multiple filopodia in all directions (light blue NCCs). The migrating cranial NCCs have intimate contact with the overlaying ectoderm and local microenvironment. (D) Cranial NCCs continue their migration toward their target sites through HH St14 in chick. During Phase II, NCCs migrate in a highly directed manner towards their target site, in this case branchial ach 2. Phase III: Entry into and invasion of the branchial arches. (E) Cranial NCCs continue to migrate and by HH St 17, they have invaded and colonized their target sites. During Phase III, NCCs transition from being loosely connected with one another to spreading out to fill the entire target site, branchial arch 2. (F) As the cranial NCCs enter the arch, they spread out from one another and display multiple filopodia in all directions (dark blue NCCs). NT, neural tube; NC, neural crest.