Abstract
In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.
Highlights
Notch is the receptor of an evolutionarily conserved cell-cell signalling pathway that controls fate acquisition in numerous processes throughout metazoan development (Kopan and Ilagan, 2009)
Discs110 large (Dlg)-GFP (Woods and Bryant, 1991) and Neuroglian-YFP (Nrg-YFP; (Genova and Fehon, 2003)), two markers of septate junction (SJ), are progressively recruited at the new pIIa-pIIb interface, immediately basal to the AJs around 25 min after anaphase, with similar kinetics as in epidermal daughters (Figure1-figure supplement 1A-B’ and E), indicating that SJ assembly occurs with similar kinetics along the new pIIa164 pIIb and epidermal cell interfaces. 165
Baz183 GFP is localised in punctate structures at the lateral pIIa-pIIb interface (Figure1 184 C-C” middle panels and orthogonal views, see Video 1). These punctate structures, which we will refer to as lateral interface clusters and are specific to the interface of Sensory organ precursors (SOPs) daughter cells, appear at the same time as the first apical Baz clusters, ~10 min after the onset of anaphase (Figure1 C-C’’). 189 Based on the distribution of Crb, atypical Protein Kinase C (aPKC) and Baz, we propose that apico-basal polarity is remodelled during SOP cytokinesis giving rise to a pIIa/pIIb interface with an atypical polarity
Summary
Notch is the receptor of an evolutionarily conserved cell-cell signalling pathway that controls fate acquisition in numerous processes throughout metazoan development (Kopan and Ilagan, 2009). Previous studies based on photobleaching and photoconversion experiments have revealed that the basal pool of Notch is the main contributor of NICD (Trylinski et al, 2017) It remains largely unknown how the two pools of Notch are targeted along the pIIa-pIIb interface to promote this private intra-lineage cell-cell communication rather than with the neighbouring epidermal 82 cells. The localisation and potential functions of Baz versus the aPKC/Par complex during cytokinesis of SOP, as well as the consequence of the polarity remodelling at mitosis on the apico-basal polarity of the pIIa-pIIb interface at the time of Notch activation, are unknown. In the SOP, the PAR complex is dismantled during cytokinesis with aPKC redistributing in intracellular apical compartments, while Baz localises into apical and lateral clusters along the pIIa126 pIIb interface together with Notch and Spdo. We propose a model in which Baz, Notch and Spdo co-cluster to favour signalling. 134
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