The Wnt Pathway Controls Cell Death Engulfment, Spindle Orientation, and Migration through CED-10/Rac

Cabello, Juan; Neukomm, Lukas J.; Günesdogan, Ufuk; Burkart, Katharina; Charette, Steve J.; Lochnit, Günter; Hengartner, Michael O.; Schnabel, Ralf

doi:10.1371/journal.pbio.1000297

Cited by 82 publications

(99 citation statements)

References 48 publications

(69 reference statements)

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“…Its simplicity, the stereotyped cell lineage, and cell movements pattern, together with its transparency, make this animal an ideal model for studying development. Genetic studies, in combination with 4D microscopy analyses, have shown that CED‐10/Rac is required for proper rotation of the mitotic spindle of some early blastomeres in the C. elegans embryo, named EMS − the endoderm and mesoderm precursor – and ABar − whose descendants form part of the pharynx − 15, 16. These mitotic spindle orientations are induced by cell signaling, from blastomeres derived from the posterior cell at the two‐cell stage embryo − termed P1 −, that triggers actin cytoskeletal reorganizations in the target cells.…”

Section: Rac/rho Small Gtpases Mediate Spindle Orientation and Cell Dmentioning

confidence: 99%

“…1). In addition to Wnt signaling, other pathways acting upstream of CED‐10/Rac, such as those described in the engulfment of the apoptotic corpses, may provide a minor contribution to embryonic cell spindle orientation 16, 18 (Fig. 1).…”

Section: Rac/rho Small Gtpases Mediate Spindle Orientation and Cell Dmentioning

confidence: 99%

“…In fact, phosphorylated APR‐1/APC has the ability to bind CED‐2/CrkII in a Yeast‐Two‐Hybrid assay. Although it is still unclear how apoptotic corpses signal the frizzled receptor, the physical interaction between APR‐1/APC and CED‐2/CrkII sheds light on how the cell directs GSK‐3 signaling toward the CED‐10/Rac pathway to promote cell corpse engulfment 16.(B.3) Another pathway upstream of the heterotrimeric CED‐5/Dock180, CED‐12/Elmo, CED‐2/Crk‐II GEF complex is mediated by the phosphatidylserine receptor, PSR‐1, which might act in this pathway through direct interaction with CED‐5/Dock180 and CED‐12/Elmo. However, since psr‐1 null mutants have a weaker engulfment defect than any of the ced‐2 , ced‐5 , or ced‐12 mutants, the contribution of this receptor to apoptotic corpse removal is thought to be minor 16, 66.…”

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

“…However, since psr‐1 null mutants have a weaker engulfment defect than any of the ced‐2 , ced‐5 , or ced‐12 mutants, the contribution of this receptor to apoptotic corpse removal is thought to be minor 16, 66.…”

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

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Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

et al. 2016

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Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we update the functions described for the Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here

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Section: Rac/rho Small Gtpases Mediate Spindle Orientation and Cell Dmentioning

confidence: 99%

Section: Rac/rho Small Gtpases Mediate Spindle Orientation and Cell Dmentioning

confidence: 99%

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

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Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

et al. 2016

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Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Chang

Hisamoto

2020

BioEssays

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Axon regeneration is a conserved process across the animal kingdom. Recent studies using the soil worm Caenorhabditis elegans as a model system revealed that machineries regulating engulfment of dying cells also control axon regeneration and axon debris removal. In this review, we examine the relationships between the engulfment machinery and the biological processes triggered by axon injury and subsequent axon regeneration drawn from divergent views. In one study, it was found that engulfing cells directly promote axon regeneration. In this context, CED-1 (Drosophila Draper/mouse MEGF10), an engulfment protein expressed on the surface of engulfing cells, functions as a receptor for axon debris removal and as an adhesion molecule for axon regeneration. In other studies, it was shown that those engulfment genes, previously known to function within the engulfing cells for cell corpse removal, can have a cell-autonomous "non-engulfing cell" role in axon regeneration. Together, these findings suggest that engulfment genes are repurposed for neuronal regeneration by acting in both engulfing cells and regenerating neurons.

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Wnt‐signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans

Ackley

2013

Developmental Neurobiology

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During the development of the nervous system, neurons encounter signals that inform their outgrowth and polarization. Understanding how these signals combinatorially function to pattern the nervous system is of considerable interest to developmental neurobiologists. The Wnt ligands and their receptors have been well characterized in polarizing cells during asymmetric cell division. The planar cell polarity (PCP) pathway is also critical for cell polarization in the plane of an epithelium. The core set of PCP genes include members of the conserved Wnt signaling pathway, such as Frizzled and Disheveled, but also the cadherin-domain protein Flamingo. In Drosophila, the Fat and Dachsous cadherins also function in PCP, but in parallel to the core PCP components. C. elegans also have two Fat-like and one Dachsous-like cadherins, at least one of which, cdh-4, contributes to neural development. In C. elegans Wnt ligands and the conserved PCP genes have been shown to regulate a number of different events, including embryonic cell polarity, vulval morphogenesis and cell migration. As is also observed in vertebrates, the Wnt and PCP genes appear to function to primarily provide information about the anterior to posterior axis of development. Here we review the recent work describing how mutations in the Wnt and core PCP genes affect axon guidance and synaptogenesis in C. elegans.

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The Wnt Pathway Controls Cell Death Engulfment, Spindle Orientation, and Migration through CED-10/Rac

Abstract: Specificity in Wnt-mediated developmental processes, such as directional cell cleavage, migration, and engulfment of dead cells in C. elegans, arises from the use of distinct Wnt pathway signalling modules.

Cited by 82 publications

References 48 publications

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Wnt‐signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans

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