Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination.

Schweitzer, Ronen; Shaharabany, Miriam; Seger, Rony; Shilo, Ben‐Zion

doi:10.1101/gad.9.12.1518

Cited by 305 publications

(228 citation statements)

References 59 publications

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“…UAS‐Flybow 1.1 [Bloomington Drosophila Stock Centre (BDSC): 35537, (Hadjieconomou et al , 2011)], UAS‐StGFP ( UAS‐Stinger , (Barolo et al , 2000), gift from M. Landgraf), UAS‐Dcr2 ( UAS‐Dicer2 , (Dietzl et al , 2007), gift from I. Salecker), UAS‐Ret [ UAS‐Ret‐3xFLAG‐6xHis (Kallijarvi et al , 2012)]; UAS‐upd1 (Jiang et al , 2009; gift from J. Cordero); UAS‐sspitz [Schweitzer et al , 1995; gift from J. Treisman); UAS‐wg ( UAS‐wg::HA , BDSC:5918); UAS‐sgg DN ( UAS‐sgg.A81T , BDSC: 5360, (Bourouis, 2002)]; UAS‐dsh DN ( UAS‐dshΔB21‐2 , (Axelrod et al , 1998), gift from J. Axelrod); UAS‐pan DN (van de Wetering et al , 1997; gift from F.J. Díaz‐Benjumea); UAS‐Src42A CA (BDSC: 6410); UAS‐Dcr2 (VDRC Stock Centre: 60007); UAS‐Ret‐RNAi (VDRC: GD 843); UAS‐dsh‐RNAi (VDRC: KK 101525); UAS‐Src42A‐RNAi (VDRC:KK 100708); UAS‐Src64B‐RNAi (VDRC: GD 35252), UAS‐Fak (Palmer et al , 1999). …”

Section: Methodsmentioning

confidence: 99%

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

et al. 2017

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Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss‐of‐function disorders such as Hirschsprung disease.

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Section: Methodsmentioning

confidence: 99%

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

et al. 2017

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“…Rhomboid mutants show increased vesicular Wingless staining in the posterior compartment, suggesting that Rhomboid is required for Wingless degradation posteriorly (Dubois et al 2001). Notably, Rhomboid activates the EGFR ligand Spitz (Schweitzer et al 1995;Urban et al 2001;Tsruya et al 2002), and EGFR mutants also show increased posterior Wingless staining (Dubois et al 2001). Therefore, Hedgehog and EGFR signaling limit the Wingless gradient by upregulating Wingless degradation.…”

Section: Modifying the Gradient: Creating Gradient Asymmetrymentioning

confidence: 97%

When cell biology meets development: endocytic regulation of signaling pathways

2002

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“…Consequently, to establish whether a particular rhomboid can cleave Spitz, it is necessary to look for the presence of a cleaved product in cell lysates as well as in medium samples. However, the detection of a cleaved intracellular product is complicated by the complex protein band pattern that results from the extensive glycosylation of Spitz (Schweitzer et al, 1995;Urban et al, 2001Urban et al, , 2002a. To circumvent this problem, we generated myc-tagged Spitz from which amino acids 31-77 had been deleted (named DSpitz), thereby removing one potential N-glycosylation site and 21 possible O-glycosylation sites.…”

Section: Tgrom1 Tgrom2 and Tgrom5 Are Active Proteasesmentioning

confidence: 99%

Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion

Dowse

Pascall

Brown

et al. 2005

International Journal for Parasitology

112

130

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Apicomplexan parasites secrete transmembrane (TM) adhesive proteins as part of the process leading to host cell attachment and invasion. These microneme proteins are cleaved in their TM domains by an unidentified protease termed microneme protein protease 1 (MPP1). The cleavage site sequence (IAYGG), mapped in the Toxoplasma gondii microneme proteins TgMIC2 and TgMIC6, is conserved in microneme proteins of other apicomplexans including Plasmodium species. We report here the characterisation of novel T. gondii proteins belonging to the rhomboid family of intramembrane-cleaving serine proteases. T. gondii possesses six genes encoding rhomboid-like proteins. Four are localised along the secretory pathway and therefore constitute possible candidates for MPP1 activity. Toxoplasma rhomboids TgROM1, TgROM2 and TgROM5 cleave the TM domain of Drosophila Spitz, an established substrate for rhomboids from several species, demonstrating that they are active proteases. In addition, TgROM2 cleaves chimeric proteins that contain the TM domains of TgMIC2 and TgMIC12. q

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Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination.

Abstract: The spitz gene encoding a TGF-~ homolog, has been shown to affect a subset of developmental processes that are similar to those regulated by DER, the Drosophila EGF receptor homolog. This work demonstrates that

Cited by 305 publications

References 59 publications

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

When cell biology meets development: endocytic regulation of signaling pathways

Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion

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