Eph/ephrins and N-cadherin coordinate to control the pattern of sympathetic ganglia

Abstract

Previous studies have suggested that the segmental pattern of neural-crest-derived sympathetic ganglia arises as a direct result of signals that restrict neural crest cell migratory streams through rostral somite halves. We recently showed that the spatiotemporal pattern of chick sympathetic ganglia formation is a two-phase process. Neural crest cells migrate laterally to the dorsal aorta, then surprisingly spread out in the longitudinal direction, before sorting into discrete ganglia. Here, we investigate the function of two families of molecules that are thought to regulate cell sorting and aggregation. By blocking Eph/ephrins or N-cadherin function, we measure changes in neural crest cell migratory behaviors that lead to alterations in sympathetic ganglia formation using a recently developed sagittal slice explant culture and 3D confocal time-lapse imaging. Our results demonstrate that local inhibitory interactions within inter-ganglionic regions, mediated by Eph/ephrins, and adhesive cell-cell contacts at ganglia sites, mediated by N-cadherin, coordinate to sculpt discrete sympathetic ganglia.

CXCR4 Controls Ventral Migration of Sympathetic Precursor Cells

“…Sagittal cryostat sections were obtained at 10 m thickness. Embryos for whole-mount staining and immunohistochemistry were fixed as above and processed as in Kasemeier-Kulesa et al (2006). Primary antibodies included the following: HNK-1 (NCC marker), TH (tyrosine hydroxylase) (sympathetic neurons), and BEN (neuronal marker) from Developmental Studies Hybridoma Bank (University of Iowa), and Tuj1 (neuronal marker; R&D Systems).…”

“…We hypothesized that temporal differences could also pattern the relative distribution and contribution of neural and progenitor cell populations in the immature SGs. From previous work in our laboratories, we identified a novel late subpopulation of NCCs that migrates through the rostral somite and directly targets the region between two incipient SGs, before coalescing with one of the two SGs (Kasemeier-Kulesa et al, 2006). To further investigate the fate of these temporally distinct migratory waves, we differentially labeled early and late delaminating NCCs and determined their identity within the SGs.…”

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…Firstly, trunk NC cells electroporated with moderate quantities of N-cadherin cDNA do migrate normally toward the ventral side of the embryo and form sympathetic ganglia. 96 Conversely, excess of cadherin-7 or cadherin-11 which are normally expressed by migrating NC cells also perturb delamination and/or migration, indicating that Contrary to epithelial cell models, NC cell EMT is not accompanied by a switch from a preferential laminin adhesion to fibronectin adhesion. Chick trunk NC cells show equal adhesion to fibronectin and laminin (at least laminin-111 also known as laminin-1) prior to and after initiation of migration, and laminin was found to promote rapid cell migration as efficiently as fibronectin.…”

Coordinated Action of N-CAM, N-cadherin, EphA4, and ephrinB2 Translates Genetic Prepatterns into Structure during Somitogenesis in Chick

“…A plausible mechanism is that pairing of complementary Ephs and ephrins on apposing cells triggers bidirectional signaling, which results in the local collapse of the actin cytoskeleton in both cells near their point of contact (Harbott and Nobes, 2005). This collapse then locally disrupts the condensation and pairing of cell adhesion molecules like N-CAM and N-cadherin, which reduces, but need not completely eliminate, the strength of their homotypic intercellular binding (as suggested in Kasemeier- Kulesa et al, 2006;Cooke et al, 2005). Thus EphA4-ephrinB2 "repulsion" in somites may actually result from a reduction in effective cell-cell adhesion.…”