scholarly journals Caenorhabditis elegansLET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells

2021 ◽  
Author(s):  
Amalia Riga ◽  
Janine Cravo ◽  
Ruben Schmidt ◽  
Helena R. Pires ◽  
Victoria G. Castiglioni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Postembryonic Development ◽  
Cell Outgrowth ◽  
C Elegans ◽  
Cellular Processes ◽  
Directed Cell Migration ◽  
Seam Cell ◽  
Discs Large ◽  
Rho Family Gtpases ◽  
Inducible Protein

AbstractThe conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. InC. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is mediated at least in part by the junctional component DLG-1 discs large, which appears to restrict protrusive activity to the apical domain. Finally, we demonstrate that the Rho-family GTPases CED-10 Rac and CDC-42 can regulate seam cell outgrowth and may also function downstream of LET-413. Our data uncover multiple essential functions for LET-413 in larval development and shed new light on the regulation of polarized outgrowth of the seam cells.

scholarly journals Caenorhabditis elegans LET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (10) ◽  
pp. e1009856
Author(s):  
Amalia Riga ◽  
Janine Cravo ◽  
Ruben Schmidt ◽  
Helena R. Pires ◽  
Victoria G. Castiglioni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Postembryonic Development ◽  
Epithelial Polarity ◽  
Adapter Protein ◽  
Cellular Processes ◽  
Directed Cell Migration ◽  
Seam Cell ◽  
Discs Large ◽  
Inducible Protein

The conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. In C. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is likely mediated largely by the junctional component DLG-1 discs large, which we demonstrate is also essential for directed outgrowth of the seam cells. Our data uncover multiple essential functions for LET-413 in larval development and show that the polarized outgrowth of the epithelial seam cells is controlled by LET-413 Scribble and DLG-1 Discs large.

scholarly journals Epidermal PAR-6 and PKC-3 are essential for postembryonic development of Caenorhabditis elegans and control non-centrosomal microtubule organization

2020 ◽  
Author(s):  
Victoria G. Castiglioni ◽  
Helena R. Pires ◽  
Rodrigo Rosas Bertolini ◽  
Amalia Riga ◽  
Jana Kerver ◽  
...  
Keyword(s):  
Cell Types ◽  
Postembryonic Development ◽  
Microtubule Organization ◽  
Par Proteins ◽  
C Elegans ◽  
Seam Cell ◽  
Broad Variety ◽  
Animal Growth ◽  
Inducible Protein ◽  
And Control

AbstractThe cortical polarity regulators PAR-6, PKC-3 and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals, from the first asymmetric division of the C. elegans zygote to apical–basal polarization of epithelial cells. In C. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using auxin-inducible protein depletion, we here show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. We also demonstrate that PAR-6 and PKC-3 are required in the epidermal epithelium to support animal growth and molting, and the proper timing and pattern of seam cell divisions. Finally, we uncovered a novel role for PAR-6 in controlling the organization of non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and microtubule defects in a noca-1 mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.SummaryUsing inducible protein degradation, we show that PAR-6 and PKC-3/aPKC are essential for postembryonic development of C. elegans and control the organization of non-centrosomal microtubule bundles in the epidermis, likely through recruitment of NOCA-1/Ninein.

scholarly journals Epidermal PAR-6 and PKC-3 are essential for larval development of C. elegans and organize non-centrosomal microtubules

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Victoria G Castiglioni ◽  
Helena R Pires ◽  
Rodrigo Rosas Bertolini ◽  
Amalia Riga ◽  
Jana Kerver ◽  
...  
Keyword(s):  
Larval Development ◽  
Cell Types ◽  
Postembryonic Development ◽  
Microtubule Organization ◽  
Par Proteins ◽  
C Elegans ◽  
Seam Cell ◽  
Broad Variety ◽  
Animal Growth ◽  
Inducible Protein

The cortical polarity regulators PAR-6, PKC-3, and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals. In C. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using inducible protein degradation, we show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. PAR-6 and PKC-3 are required in the epidermal epithelium for animal growth, molting, and the proper pattern of seam-cell divisions. Finally, we uncovered a novel role for PAR-6 in organizing non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and defects in a noca-1 mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.

The regulation of cell migration by PTEN

2005 ◽  
Vol 33 (6) ◽  
pp. 1507-1508 ◽  
Author(s):  
N.R. Leslie ◽  
X. Yang ◽  
C.P. Downes ◽  
C.J. Weijer
Keyword(s):  
Cell Migration ◽  
Phosphatase Activity ◽  
Tumour Suppressor ◽  
Chromosome 10 ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Directed Cell Migration ◽  
Phosphoinositide 3 Kinase ◽  
Phosphatase And Tensin Homologue

In vertebrates, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) regulates many cellular processes through its PtdIns(3,4,5)P3 lipid phosphatase activity, antagonizing PI3K (phosphoinositide 3-kinase) signalling. Given the important role of PI3Ks in the regulation of directed cell migration and the role of PTEN as an inhibitor of migration, it is somewhat surprising that data now indicate that PTEN is able to regulate cell migration independent of its lipid phosphatase activity. Here, we discuss the role of PTEN in the regulation of cell migration.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

A Deficiency Screen for Zygotic Loci Required for Establishment and Patterning of the Epidermis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 185-206 ◽  
Author(s):  
Rebecca M Terns ◽  
Peggy Kroll-Conner ◽  
Jiangwen Zhu ◽  
Sooyoun Chung ◽  
Joel H Rothman
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Epidermal Cells ◽  
Epidermal Differentiation ◽  
Apparent Effect ◽  
Internal Organs ◽  
C Elegans ◽  
Seam Cell ◽  
Genomic Regions ◽  
Caenorhabditis Elegans Genome

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ∼67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

scholarly journals Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning

2021 ◽  
Vol 22 (10) ◽  
pp. 5056
Author(s):  
Tulio L. Campos ◽  
Pasi K. Korhonen ◽  
Neil D. Young
Keyword(s):  
Machine Learning ◽  
Experimental Studies ◽  
Essential Genes ◽  
Subcellular Localisation ◽  
Cross Prediction ◽  
Gene Essentiality ◽  
C Elegans ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
The Cross

Experimental studies of Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular and cellular processes in metazoans at large. Since the publication of their genomes, functional genomic investigations have identified genes that are essential or non-essential for survival in each species. Recently, a range of features linked to gene essentiality have been inferred using a machine learning (ML)-based approach, allowing essentiality predictions within a species. Nevertheless, predictions between species are still elusive. Here, we undertake a comprehensive study using ML to discover and validate features of essential genes common to both C. elegans and D. melanogaster. We demonstrate that the cross-species prediction of gene essentiality is possible using a subset of features linked to nucleotide/protein sequences, protein orthology and subcellular localisation, single-cell RNA-seq, and histone methylation markers. Complementary analyses showed that essential genes are enriched for transcription and translation functions and are preferentially located away from heterochromatin regions of C. elegans and D. melanogaster chromosomes. The present work should enable the cross-prediction of essential genes between model and non-model metazoans.

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