scholarly journals PCH-2TRIP13 regulates spindle checkpoint strength

2018 ◽  
Author(s):  
Lénaïg Défachelles ◽  
Anna E. Russo ◽  
Christian R. Nelson ◽  
Needhi Bhalla
Keyword(s):  
Cell Volume ◽  
Cell Fate ◽  
Spindle Checkpoint ◽  
Early Embryo ◽  
Precursor Cells ◽  
Developmental Competence ◽  
Active Conformation ◽  
Aaa Atpase ◽  
C Elegans ◽  
Early Embryos

ABSTRACTSpindle checkpoint strength is dictated by three criteria: the number of unattached kinetochores, cell volume and cell fate. We show that the conserved AAA-ATPase, PCH-2/TRIP13, which remodels the checkpoint effector Mad2 from an active conformation to an inactive one, controls checkpoint strength in C. elegans. When we manipulate embryos to decrease cell volume, PCH-2 is no longer required for the spindle checkpoint or recruitment of Mad2 at unattached kinetochores. This role in checkpoint strength is not limited to large cells: the stronger checkpoint in germline precursor cells also depends on PCH-2. PCH-2 is enriched in germline precursor cells and this enrichment relies on conserved factors that induce asymmetry in the early embryo. Finally, the stronger checkpoint in germline precursor cells is regulated by CMT-1, the ortholog of p31comet, which is required for both PCH-2’s localization to unattached kinetochores and its enrichment in germline precursor cells. Thus, PCH-2, likely by regulating the availability of inactive Mad2 at and near unattached kinetochores, governs checkpoint strength. This role may be specifically relevant in scenarios where maintaining genomic stability is particularly challenging, such as in oocytes and early embryos enlarged for developmental competence and germline cells that maintain immortality.

scholarly journals The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength

2020 ◽  
Vol 31 (20) ◽  
pp. 2219-2233
Author(s):  
Lénaïg Défachelles ◽  
Anna E. Russo ◽  
Christian R. Nelson ◽  
Needhi Bhalla
Keyword(s):  
Cell Cycle ◽  
Cell Volume ◽  
Cell Fate ◽  
Spindle Checkpoint ◽  
Early Embryogenesis ◽  
Aaa Atpase ◽  
Cell Cycle Delay ◽  
C Elegans

The length of the cell cycle delay imposed by the spindle checkpoint, also referred to as the spindle checkpoint strength, is controlled by the number of unattached kinetochores, cell volume, and cell fate. We show that PCH-2, a highly conserved AAA-ATPase, controls checkpoint strength during early embryogenesis in C. elegans.

The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3815-3826 ◽  
Author(s):  
B. Bowerman ◽  
M.K. Ingram ◽  
C.P. Hunter
Keyword(s):  
Cell Fate ◽  
Expression Patterns ◽  
Control Cell ◽  
Gene Products ◽  
Cell Fate Specification ◽  
Loss Of Function ◽  
C Elegans ◽  
Embryonic Polarity ◽  
Early Embryos ◽  
Anterior Posterior

After fertilization in C. elegans, activities encoded by the maternally expressed par genes appear to establish cellular and embryonic polarity. Loss-of-function mutations in the par genes disrupt anterior-posterior (a-p) asymmetries in early embryos and result in highly abnormal patterns of cell fate. Little is known about how the early asymmetry defects are related to the cell fate patterning defects in par mutant embryos, or about how the par gene products affect the localization and activities of developmental regulators known to specify the cell fate patterns made by individual blastomeres. Examples of such regulators of blastomere identity include the maternal proteins MEX-3 and GLP-1, expressed at high levels anteriorly, and SKN-1 and PAL-1, expressed at high levels posteriorly in early embryos. To better define par gene functions, we examined the expression patterns of MEX-3, PAL-1 and SKN-1, and we analyzed mex-3, pal-1, skn-1 and glp-1 activities in par mutant embryos. We have found that mutational inactivation of each par gene results in a unique phenotype, but in no case do we observe a complete loss of a-p asymmetry. We conclude that no one par gene is required for all a-p asymmetry and we suggest that, in some cases, the par genes act independently of each other to control cell fate patterning and polarity. Finally, we discuss the implications of our findings for understanding how the initial establishment of polarity in the zygote by the par gene products leads to the proper localization of more specifically acting regulators of blastomere identity.

scholarly journals Cell fate patterning during C. elegans vulval development

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 9-18 ◽  
Author(s):  
Russell J. Hill ◽  
Paul W. Sternberg
Keyword(s):  
Cell Fate ◽  
Short Range ◽  
Precursor Cells ◽  
Cell Fates ◽  
Vulval Development ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Combined Action ◽  
Anchor Cell ◽  
Inductive Signal

Precursor cells of the vulva of the C. elegans hermaphrodite choose between two vulval cell fates (1° and 2°) and a non-vulval epidermal fate (3°) in response to three intercellular signals. An inductive signal produced by the anchor cell induces the vulval precursors to assume the 1° and 2° vulval fates. This inductive signal is an EGF-like growth factor encoded by the gene lin-3. An inhibitory signal mediated by lin-15, and which may originate from the surrounding epidermis, prevents the vulval precursors from assuming vulval fates in the absence of the inductive signal. A short range lateral signal, which acts through the gene lin-12, regulates the pattern of 1° and 2° fates assumed by the induced vulval precursors. The combined action of the three signals precisely directs the six vulval precursors to adopt a 3° 3° 2° 1° 2 ° 3° pattern of fates. The amount of inductive signal produced by the anchor cell appears to determine the number or vulval precursors that assume vulval fates. The three induced vulval precursors most proximal to the anchor cell are proposed to adopt the 2° 1° 2° pattern of fates in response to a gradient of the inductive signal and also in response to lateral signalling that inhibits adjacent vulval precursor cells from both assuming the 1° fate.

The nematode even-skipped homolog vab-7 regulates gonad and vulva position in Pristionchus pacificus

Development ◽  
2001 ◽  
Vol 128 (2) ◽  
pp. 253-261 ◽  
Author(s):  
B. Jungblut ◽  
R.J. Sommer
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Nematode Species ◽  
Cellular Level ◽  
Precursor Cells ◽  
Developmental Competence ◽  
Pristionchus Pacificus ◽  
Posterior Displacement ◽  
Cell Ablation ◽  
The One

In free-living nematodes, developmental processes like the formation of the vulva, can be studied at a cellular level. Cell lineage and ablation studies have been carried out in various nematode species and multiple changes in vulval patterning have been identified. In Pristionchus pacificus, vulva formation differs from Caenorhabditis elegans with respect to several autonomous and conditional aspects of cell fate specification. To understand the molecular basis of these evolutionary changes, we have performed a genetic analysis of vulva formation in P. pacificus. Here, we describe two mutants where the vulva is shifted posteriorly, affecting which precursor cells will form vulval tissue in P. pacificus. Mutant animals show a concomitant posterior displacement of the gonadal anchor cell, indicating that the gonad and the vulva are affected in a similar way. We show that mutations in the even-skipped homolog of nematodes, vab-7, cause these posterior displacements. In addition, cell ablation studies in the vab-7 mutant indicate that the altered position of the gonad not only changes the cell fate pattern but also the developmental competence of vulval precursor cells. Investigation of Cel-vab-7 mutant animals showed a similar but weaker vulva defective phenotype to the one described for Ppa-vab-7.

The Caenorhabditis elegans polarity gene ooc-5 encodes a Torsin-related protein of the AAA ATPase superfamily

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4645-4656 ◽  
Author(s):  
Stephen E. Basham ◽  
Lesilee S. Rose
Keyword(s):  
Cell Fate ◽  
Protein Complexes ◽  
Sequence Similarity ◽  
Normal Function ◽  
Par Proteins ◽  
Torsion Dystonia ◽  
Aaa Atpase ◽  
C Elegans ◽  
Fate Determinants ◽  
Cell Fate Determinants

The PAR proteins are required for polarity and asymmetric localization of cell fate determinants in C. elegans embryos. In addition, several of the PAR proteins are conserved and localized asymmetrically in polarized cells in Drosophila, Xenopus and mammals. We have previously shown that ooc-5 and ooc-3 mutations result in defects in spindle orientation and polarity in early C. elegans embryos. In particular, mutations in these genes affect the re-establishment of PAR protein asymmetry in the P1 cell of two-cell embryos. We now report that ooc-5 encodes a putative ATPase of the Clp/Hsp100 and AAA superfamilies of proteins, with highest sequence similarity to Torsin proteins; the gene for human Torsin A is mutated in individuals with early-onset torsion dystonia, a neuromuscular disease. Although Clp/Hsp100 and AAA family proteins have roles in diverse cellular activities, many are involved in the assembly or disassembly of proteins or protein complexes; thus, OOC-5 may function as a chaperone. OOC-5 protein co-localizes with a marker of the endoplasmic reticulum in all blastomeres of the early C. elegans embryo, in a pattern indistinguishable from that of OOC-3 protein. Furthermore, OOC-5 localization depends on the normal function of the ooc-3 gene. These results suggest that OOC-3 and OOC-5 function in the secretion of proteins required for the localization of PAR proteins in the P1 cell, and may have implications for the study of torsion dystonia.

scholarly journals LET-711, the Caenorhabditis elegans NOT1 Ortholog, Is Required for Spindle Positioning and Regulation of Microtubule Length in Embryos

2006 ◽  
Vol 17 (11) ◽  
pp. 4911-4924 ◽  
Author(s):  
Leah R. DeBella ◽  
Adam Hayashi ◽  
Lesilee S. Rose
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Regulation Of Gene Expression ◽  
Early Embryo ◽  
Cell Cortex ◽  
Loss Of Function ◽  
Wild Type ◽  
Spindle Positioning ◽  
C Elegans ◽  
Associated Proteins

Spindle positioning is essential for the segregation of cell fate determinants during asymmetric division, as well as for proper cellular arrangements during development. In Caenorhabditis elegans embryos, spindle positioning depends on interactions between the astral microtubules and the cell cortex. Here we show that let-711 is required for spindle positioning in the early embryo. Strong loss of let-711 function leads to sterility, whereas partial loss of function results in embryos with defects in the centration and rotation movements that position the first mitotic spindle. let-711 mutant embryos have longer microtubules that are more cold-stable than in wild type, a phenotype opposite to the short microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG-9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and rotation defects of both single mutants. let-711 mutant embryos also have larger than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared with wild type. Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals. We therefore propose that LET-711 inhibits the expression of ZYG-9 and potentially other centrosome-associated proteins, in order to maintain normal centrosome size and microtubule dynamics during early embryonic divisions.

scholarly journals Golgi localization of the LIN-2/7/10 complex points to a role in basolateral secretion of LET-23 EGFR in the C. elegans vulval precursor cells

Development ◽  
2021 ◽  
pp. dev.194167
Author(s):  
Kimberley D. Gauthier ◽  
Christian E. Rocheleau
Keyword(s):  
Cell Fate ◽  
Spatial Organization ◽  
Basolateral Membrane ◽  
Growth Factor Receptor ◽  
Precursor Cells ◽  
C Elegans ◽  
Receptor Localization ◽  
Epidermal Growth ◽  
Complex Forms

The evolutionarily conserved LIN-2 (CASK)/LIN-7 (Lin7A-C)/LIN-10 (APBA1) complex plays an important role in regulating spatial organization of membrane proteins and signaling components. In C. elegans, the complex is essential for development of the vulva by promoting the localization of the sole Epidermal Growth Factor Receptor (EGFR) orthologue, LET-23, to the basolateral membrane of the vulva precursor cells (VPCs) where it can specify the vulval cell fate. To understand how the LIN-2/7/10 complex regulates receptor localization, we determined its expression and localization during vulva development. We found that LIN-7 colocalizes with LET-23 EGFR at the basolateral membrane, whereas the LIN-2/7/10 complex colocalizes with LET-23 EGFR at cytoplasmic punctae, that mostly overlap with the Golgi. Furthermore, LIN-10 recruits LIN-2, which in turn recruits LIN-7. We demonstrate that the complex forms in vivo with particularly strong interaction and colocalization between LIN-2 and LIN-7 consistent with their forming a subcomplex. Thus, the LIN-2/7/10 complex forms on the Golgi where it likely targets LET-23 EGFR trafficking to the basolateral membrane rather than functioning as a tether.

Novel cell-cell interactions during vulva development in Pristionchus pacificus

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3295-3303 ◽  
Author(s):  
B. Jungblut ◽  
R.J. Sommer
Keyword(s):  
Precursor Cells ◽  
Cell Interactions ◽  
Developmental Competence ◽  
Specific Response ◽  
Pristionchus Pacificus ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Continuous Interaction ◽  
One Step ◽  
Cell Cell

Vulva development differs between Caenorhabditis elegans and Pristionchus pacificus in several ways. Seven of 12 ventral epidermal cells in P. pacificus die of apoptosis, whereas homologous cells in C. elegans fuse with the hypodermal syncytium. Vulva induction is a one-step process in C. elegans, but requires a continuous interaction between the gonad and the epidermis in P. pacificus. Here we describe several novel cell-cell interactions in P. pacificus, focusing on the vulva precursor cell P8.p and the mesoblast M. P8.p in P. pacificus, unlike its homologous cell in C. elegans, is incompetent to respond to gonadal signaling in the absence of other vulva precursor cells, but can respond to lateral signaling from a neighboring vulval precursor. P8.p provides an inhibitory signal that determines the developmental competence of P(5,7).p. This lateral inhibition acts via the mesoblast M and is regulated by the homeotic gene Ppa-mab-5. In Ppa-mab-5 mutants, M is misspecified and provides inductive signaling to the vulval precursor cells, including P8.p. Taken together, vulva development in P. pacificus displays novel cell-cell interactions involving the mesoblast M and P8.p. In particular, P8.p represents a new ventral epidermal cell type, which is characterized by novel interactions and a specific response to gonadal signaling.

scholarly journals MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 747-759 ◽  
Author(s):  
Nancy N. Huang ◽  
Darcy E. Mootz ◽  
Albertha J. M. Walhout ◽  
Marc Vidal ◽  
Craig P. Hunter
Keyword(s):  
Cell Fate ◽  
Spatial Information ◽  
Zinc Finger Protein ◽  
Early Embryo ◽  
Rna Recognition Motif ◽  
Homeodomain Protein ◽  
Interacting Proteins ◽  
Cell Stage ◽  
C Elegans ◽  
Temporal And Spatial

The KH domain protein MEX-3 is central to the temporal and spatial control of PAL-1 expression in the C. elegans early embryo. PAL-1 is a Caudal-like homeodomain protein that is required to specify the fate of posterior blastomeres. While pal-1 mRNA is present throughout the oocyte and early embryo, PAL-1 protein is expressed only in posterior blastomeres, starting at the four-cell stage. To better understand how PAL-1 expression is regulated temporally and spatially, we have identified MEX-3 interacting proteins (MIPs) and characterized in detail two that are required for the patterning of PAL-1 expression. RNA interference of MEX-6, a CCCH zinc-finger protein, or SPN-4, an RNA recognition motif protein, causes PAL-1 to be expressed in all four blastomeres starting at the four-cell stage. Genetic analysis of the interactions between these mip genes and the par genes, which provide polarity information in the early embryo, defines convergent genetic pathways that regulate MEX-3 stability and activity to control the spatial pattern of PAL-1 expression. These experiments suggest that par-1 and par-4 affect distinct processes. par-1 is required for many aspects of embryonic polarity, including the restriction of MEX-3 and MEX-6 activity to the anterior blastomeres. We find that PAL-1 is not expressed in par-1 mutants, because MEX-3 and MEX-6 remain active in the posterior blastomeres. The role of par-4 is less well understood. Our analysis suggests that par-4 is required to inactivate MEX-3 at the four-cell stage. Thus, PAL-1 is not expressed in par-4 mutants because MEX-3 remains active in all blastomeres. We propose that MEX-6 and SPN-4 act with MEX-3 to translate the temporal and spatial information provided by the early acting par genes into the asymmetric expression of the cell fate determinant PAL-1.

Sign in / Sign up

Export Citation Format

Share Document