Table 1. Main assumptions in the follow-the-leader (FtL) model and CIL-CoA model, their experimental basis, and their consequences.

Model	Assumption	Experimental basis	Consequence
FtL	Heterogeneous NC population	Gene expression profiling	Population of two cell types with two independent phenotypic behaviours
FtL	Leader NC cells chemotax towards VEGF	NC move towards ectopic VEGF sources	Directional cluster movement
FtL	Follower NC cells do not chemotax towards VEGF	None
FtL	Follower NC cells move towards the nearest leader or towards collectives headed by a leader (similar to CoA)	None	Alignment and cohesion of the cluster
FtL	VEGF is homogeneously distributed along the NC path before migration	Immunohistochemistry on sections from avian embryos	VEGF gradient made possible through sequestration
FtL	VEGF is internalized by the NC cells	VEGF internalized in in vitro wounding assay of endothelial cells [37]	VEGF gradient generated by sequestration
FtL	Leader phenotype is triggered by exposure to VEGF gradient	Leader expression profile observed in trailer cells when exposed to VEGF	Adaptive cluster behaviour able to respond to ectopic VEGF
CIL-CoA	Co-Attraction: NC cells secrete a chemoattractant	Complement component C3 is expressed by NC cells in Xenopus laevis, and cells chemotax towards C3a.	Cluster cohesion
CIL-CoA	Homogeneous NC population	Similar response to signals from leader and followers (potential indication of plasticity)	Simplifying assumption
CIL-CoA	CIL	NC cells exhibit CIL in vivo and in vitro across species	Polarized cell protrusions driving cells away from the cluster
CIL-CoA	Cell velocities are aligned after contact	Phenomenological observation based on trajectory analysis of NC cells	Synchronization of cell movements in the cluster