Colonizing while migrating: how do individual enteric neural crest cells behave?

Annette J Bergner,Sonja J Mckeown,Matthew J Simpson,Hideki Enomoto,Heather M Young,Marlene M Hao,Colin R Anderson

doi:10.1186/1741-7007-12-23

Abstract

BackgroundDirected cell migration is essential for normal development. In most of the migratory cell populations that have been analyzed in detail to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. Very little is known about how individual cells behave to achieve concomitant directional migration and population of the migratory route. We examined the behavior of enteric neural crest-derived cells (ENCCs), which must both advance caudally to reach the anal end and populate each gut region.ResultsThe behavior of individual ENCCs was examined using live imaging and mice in which ENCCs express a photoconvertible protein. We show that individual ENCCs exhibit very variable directionalities and speed; as the migratory wavefront of ENCCs advances caudally, each gut region is populated primarily by some ENCCs migrating non-directionally. After populating each region, ENCCs remain migratory for at least 24 hours. Endothelin receptor type B (EDNRB) signaling is known to be essential for the normal advance of the ENCC population. We now show that perturbation of EDNRB principally affects individual ENCC speed rather than directionality. The trajectories of solitary ENCCs, which occur transiently at the wavefront, were consistent with an unbiased random walk and so cell-cell contact is essential for directional migration. ENCCs migrate in close association with neurites. We showed that although ENCCs often use neurites as substrates, ENCCs lead the way, neurites are not required for chain formation and neurite growth is more directional than the migration of ENCCs as a whole.ConclusionsEach gut region is initially populated by sub-populations of ENCCs migrating non-directionally, rather than stopping. This might provide a mechanism for ensuring a uniform density of ENCCs along the growing gut.

Highlights

Directed cell migration is essential for normal development
enteric neural crest-derived cells (ENCCs) migrate in chains with high cell-cell contact [21,23,24,28], and so little is known about how individual ENCCs behave to ensure that all regions of the gut are evenly populated with ENCCs
To examine how ENCC behavior varies with location, speed, overall direction of migration, tortuosity and rate of caudal advance of individual ENCCs were determined in 150 μm bins from the migratory wavefront for up to 1,200 μm rostrally (Figure 1)

Summary

Introduction

Directed cell migration is essential for normal development. In most of the migratory cell populations that have been analyzed in detail to date, all of the cells migrate as a collective from one location to another. Previous imaging studies of cranial neural crest cells in Xenopus and chick embryos have revealed the organization of the cells as they migrate, the rules guiding their behavior and some of the molecular bases of the interactions [1,2] In both species, the cells move as a collective from one location to another; in chick embryos, there is a “follow the leader” chain migration in which the spatial order of cells is retained [3,4,5,6,7]. ENCCs migrate in chains with high cell-cell contact [21,23,24,28], and so little is known about how individual ENCCs behave to ensure that all regions of the gut are evenly populated with ENCCs. We had previously assumed that each gut region is colonized by sub-populations of ENCCs stopping as the wavefront of ENCCs moves caudally [23]. The migration of ENCCs is an excellent model to examine how individual cells behave in a population that both migrates directionally and populates regions along the migratory route

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