Abstract
Developmental patterning involves the progressive subdivision of tissue into different cell types by invoking different genetic programs. In particular, cell-cell signaling is a universally deployed means of specifying distinct cell fates in adjacent cells. For this mechanism to be effective, it is essential that an asymmetry be established in the signaling and responding capacities of the participating cells. Here we focus on the regulatory mechanisms underlying the role of the neuralized gene and its protein product in establishing and maintaining asymmetry of signaling through the Notch pathway. The context is the classical process of “lateral inhibition” within Drosophila proneural clusters, which is responsible for distinguishing the sensory organ precursor (SOP) and non-SOP fates among adjacent cells. We find that neur is directly regulated in proneural clusters by both proneural transcriptional activators and Enhancer of split basic helix-loop-helix repressors (bHLH-Rs), via two separate cis-regulatory modules within the neur locus. We show that this bHLH-R regulation is required to prevent the early, pre-SOP expression of neur from being maintained in a subset of non-SOPs following SOP specification. Lastly, we demonstrate that Neur activity in the SOP is required to inhibit, in a cell non-autonomous manner, both neur expression and Neur function in non-SOPs, thus helping to secure the robust establishment of distinct cell identities within the developing proneural cluster.
Highlights
The specification of discrete cell identities during metazoan development often requires the establishment of disparate genetic programs in adjacent cells
Much of the process of animal development is concerned with giving cells specific instructions as to what type of cell they are to become—their “fate”
One cell might send a signal to its neighbors that inhibits them from adopting the same fate as itself
Summary
The specification of discrete cell identities during metazoan development often requires the establishment of disparate genetic programs in adjacent cells. The Notch signaling pathway is ideally suited to this task, since it mediates direct cell-cell interactions via contact between transmembrane ligands and receptors Acting in this fashion, it is responsible for distinguishing the gene expression programs of adjacent cells in multiple developmental settings, including boundary formation between neighboring cell populations; binary cell fate specification between daughter cells in a cell lineage; and “lateral inhibition” within a cluster of cells with initially similar fate [1]. It is responsible for distinguishing the gene expression programs of adjacent cells in multiple developmental settings, including boundary formation between neighboring cell populations; binary cell fate specification between daughter cells in a cell lineage; and “lateral inhibition” within a cluster of cells with initially similar fate [1] If such binary partitioning of cell fate is to function with high fidelity, it requires the creation of strong disparities in Notch signaling and responding capacity between “sending” and “receiving” cells. One example is the classical process of lateral inhibition within proneural clusters (PNCs) in Drosophila
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