Planar cell polarity controls directional Notch signaling in the Drosophila leg

A. Capilla; R. Johnson; M. Daniels; M. Benavente; S. J. Bray; M. I. Galindo

doi:10.1242/dev.077446

Regulation of Numb during planar cell polarity establishment in the Drosophila eye

10.1101/686840 ◽

2019 ◽

Author(s):

Pedro M Domingos ◽

Andreas Jenny ◽

David del Alamo ◽

Marek Mlodzik ◽

Hermann Steller ◽

...

Keyword(s):

Notch Signaling ◽

Cell Polarity ◽

Planar Cell Polarity ◽

Asymmetric Cell Division ◽

Photoreceptor Cells ◽

Negative Regulator ◽

Transcriptional Level ◽

Loss Of Function ◽

Giant Larva ◽

Signaling Activation

ABSTRACTThe establishment of planar cell polarity (PCP) in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells, determined by a Frizzled mediated signaling event that specifies R3 and induces Delta to activate Notch signaling in the neighboring cell, specifying it as R4. Here, we investigated the role of the Notch signaling negative regulator Numb in the specification of R3/R4 fates and PCP establishment in the Drosophila eye. We observed that Numb is transiently upregulated in R3 at the time of R3/R4 specification. This regulation of Numb levels in developing photoreceptors occurs at the post-transcriptional level and is dependent on Dishevelled, an effector of Frizzled signaling, and Lethal Giant Larva. We detected PCP defects in cells homozygous for numb15, but these defects were due to a loss of function mutation in fat (fatQ805*) being present in the numb15 chromosome. However, mosaic overexpression of Numb in R4 precursors (only) caused PCP defects and numb loss-of-function had a modifying effect on the defects found in a hypomorphic dishevelled mutation. Our results suggest that Numb levels are upregulated to reinforce the bias of Notch signaling activation in the R3/R4 pair, two post-mitotic cells that are not specified by asymmetric cell division.

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The E3 Ubiquitin Ligase Mindbomb1 controls zebrafish Planar Cell Polarity

10.1101/2021.07.05.451064 ◽

2021 ◽

Author(s):

Vishnu Muraleedharan Saraswathy ◽

Priyanka Sharma ◽

Akshai Janardhana Kurup ◽

Sophie Polès ◽

Morgane Poulain ◽

...

Keyword(s):

Notch Signaling ◽

Cell Polarity ◽

Ubiquitin Ligase ◽

Protein Trafficking ◽

Planar Cell Polarity ◽

E3 Ubiquitin Ligase ◽

Notch Pathway ◽

Ring Finger ◽

Critical Event ◽

Loss Of Function

Vertebrate Delta/Notch signaling involves multiple ligands, receptors and transcription factors. Delta endocytosis – a critical event for Notch activation – is however essentially controlled by the E3 Ubiquitin ligase Mindbomb1 (Mib1). Due to its position at a molecular bottleneck of the pathway, Mib1 inactivation is often used to inhibit Notch signaling. However, recent findings indicate that the importance of Mib1 extends beyond the Notch pathway. We report an essential role of Mib1 in Planar Cell Polarity (PCP). mib1 null mutants or morphants display impaired gastrulation stage Convergence Extension (CE) movements. Comparison of different mib1 mutants and functional rescue experiments indicate that Mib1 controls CE independently of Notch. In contrast, Mib1-dependent CE defects can be rescued using the PCP downstream mediator RhoA. Mib1 regulates CE through the RING Finger domains that have been implicated in substrate ubiquitination, suggesting that Mib1 may control PCP protein trafficking. Accordingly, we show that Mib1 controls the endocytosis of the PCP component Ryk and that Ryk internalization is required for CE. Numerous morphogenetic processes involve both Notch and PCP signaling. We show that Mib1, a known Notch signaling regulator, is also an essential PCP pathway component. Care should therefore be taken when interpreting Mib1 loss of function phenotypes.

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