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

Abstract

During gastrulation in vertebrates, mesenchymal cells at the anterior end of the pre-somitic mesoderm (PSM) periodically compact, transiently epithelialize and detach from the posterior PSM to form somites. In the prevailing clock-and-wavefront model of somitogenesis, periodic gene expression, particularly of Notch and Wnt, interacts with an FGF8-based thresholding mechanism to determine cell fates. However, this model does not explain how cell determination and subsequent differentiation translates into somite morphology. In this paper, we use computer simulations of chick somitogenesis to show that experimentally-observed temporal and spatial patterns of adhesive N-CAM and N-cadherin and repulsive EphA4-ephrinB2 pairs suffice to reproduce the complex dynamic morphological changes of somitogenesis in wild-type and N-cadherin (−/−) chick, including intersomitic separation, boundary-shape evolution and sorting of misdifferentiated cells across compartment boundaries. Since different models of determination yield the same, experimentallyobserved, distribution of adhesion and repulsion molecules, the patterning is independent of the details of this mechanism.

Eph/ephrin interactions modulate muscle satellite cell motility and patterning

“…During axon outgrowth or cell migration, this repulsive response guides growth cones or cells to their final destination, where frequently a different ephrin or ephrins is expressed and promotes formation of a neuromuscular junction (Lai et al, 2001) or cessation of migration and adhesion (Halloran and Wolman, 2006;Glazier et al, 2008;Wimmer-Kleikamp et al, 2008;Lee and Daar, 2009). Other changes downstream of ephrin signaling, such as adhesion receptor clustering and changes in substrate affinity, are required for cell sorting during rhombomere and somite segmentation (Cooke et al, 2001;Tanaka et al, 2003;Glazier et al, 2008;Kemp et al, 2009;Julich et al, 2009).…”

“…Other changes downstream of ephrin signaling, such as adhesion receptor clustering and changes in substrate affinity, are required for cell sorting during rhombomere and somite segmentation (Cooke et al, 2001;Tanaka et al, 2003;Glazier et al, 2008;Kemp et al, 2009;Julich et al, 2009). Finally, in the case of interactions between stem cells and their niche, Eph/ephrin signaling has been shown to direct both homing to and activities within the niche via modifications in adhesion receptor activity and modulation of downstream signaling pathways (Stokowski et al, 2007;Arthur et al, 2010;Ting et al, 2010).…”

Ephrin-Eph signaling in embryonic tissue separation

“…2) Additional mechanisms could strengthen cohesion in the middle of the segment, perhaps involving N-cadherin and N-CAM. 98 b) In Zebrafish, which is partially tetraploid, there are 2 ephrinB2 "pseudo-alleles." Only ephrinB2a was studied, which fitted with the classical view of ligand-receptor complementarity.…”

Simulation Frameworks for Morphogenetic Problems

“…To explain the regular pattern formation in somitogenesis, Glazier et al [105] studied a clock based mechanism. A clock-and wavefront-free mechanisms for somitogenesis has been proposed [106].…”