  Multicellular organisms exhibit a high degree of structural organization with
specific cell types always occurring in characteristic locations. The
conventional framework for describing the emergence of such consistent spatial
patterns is provided by Wolpert's "French flag" paradigm. According to this
view, intra-cellular genetic regulatory mechanisms use positional information
provided by morphogen concentration gradients to differentially express
distinct fates, resulting in a characteristic pattern of differentiated cells.
However, recent experiments have shown that suppression of inter-cellular
interactions can alter these spatial patterns, suggesting that cell fates are
not exclusively determined by the regulation of gene expression by local
morphogen concentration. Using an explicit model where adjacent cells
communicate by Notch signaling, we provide a mechanistic description of how
contact-mediated interactions allow information from the cellular environment
to be incorporated into cell fate decisions. Viewing cellular differentiation
in terms of trajectories along an epigenetic landscape (as first enunciated by
Waddington), our results suggest that the contours of the landscape are moulded
differently in a cell position-dependent manner, not only by the global signal
provided by the morphogen but also by the local environment via cell-cell
interactions. We show that our results are robust with respect to different
choices of coupling between the inter-cellular signaling apparatus and the
intra-cellular gene regulatory dynamics. Indeed, we show that the broad
features can be observed even in abstract spin models. Our work reconciles
interaction-mediated self-organized pattern formation with boundary-organized
mechanisms involving signals that break symmetry.
