Delivering the Lateral Inhibition Punchline: It's All About the Timing

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science Signaling (Impact Factor: 6.28). 10/2010; 3(145):pe38. DOI: 10.1126/scisignal.3145pe38
Source: PubMed


Experimental and theoretical biologists have long been fascinated with the emergence of self-organizing patterns in developing organisms, and much attention has focused on Notch-mediated lateral inhibition. Within sheets of cells that may adopt either of two possible cell fates, lateral inhibition establishes patterns through the activity of a negative intercellular feedback loop involving the receptor, Notch, and its ligands Delta or Serrate. Despite a long history of intensive study in Drosophila, where the mechanism was first described, as well as in other organisms, new work continues to yield important insights. Mathematical modeling, combined with biological analyses, has now shed light on two features of the process: how antagonistic and activating ligand-receptor interactions work together to accelerate inhibition and ensure fidelity, and how filopodial dynamics contribute to the observed pattern refinement and spacing.

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    • "The expression of these activators maintains neural competency in groups of otherwise equipotential cells, the proneural clusters (PNCs). This broad expression of Ato/ASC is later refined by the HES repressors in a process called lateral inhibition [22]–[24], during which the presumptive R8/SOP activates Notch to elicit HES expression in all other cells of the PNC. The HES repressors then antagonize Ato/ASC, thereby ensuring the specification (birth) of a single R8/SOP from each PNC, which is critical for proper structure and patterning of the eye and bristles. "
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    • "However, our cell autonomy results suggest that SMP-1 functions with PLX-1 in cis to regulate subcellular localization of PLX-1. It has been reported that some transmembrane ligands, including Sema6A, function in the same cells as their receptors to inhibit receptor activation by competing with the trans-expressed ligands or through unknown mechanisms (Axelrod, 2010; Haklai-Topper et al., 2010; Yaron and Sprinzak, 2012). Our results are a demonstration that a semaphorin activates its receptor in the same cell. "
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    • "Timing and spatial distribution of gene expression in the rabbit support the evidence of a functional significance of the BMP–BLIMP1 connection for PGC lineage segregation in general, but single BLIMP1-positive cells surrounded by complete ring of BLIMP1-negative ones at stages 2 and 3 (cf. Fig. 5) suggest that the initial step for the successful segregation of PGCs may be a lateral inhibition event in single cells similar to neuroblast generation in Drosophila as the result of the Notch–Delta signaling pathway (Axelrod 2010). Complexity is added to the process as it occurs almost simultaneously with the singling out of presumptive mesoderm cells within the epiblast layer in the same location, the posterior gastrula extension (PGE) area: 10 to 15 single epiblast cells of the PGE express the mesodermal master control gene brachyury at stage 2 (Viebahn et al. 2002), i.e., at a time when the first few BLIMP1-positive epiblast cells appear at the posterior periphery of the PGE area; at stage 3, a handful of BLIMP1-positive cells occupy the very same region as the strong brachyury expression domain overlying the posterior half of the emerging primitive streak (cf. "
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