scholarly journals Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal coordination between cell-cycle control and vulval development

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 4049-4060 ◽  
Author(s):  
D.S. Fay ◽  
M. Han
Keyword(s):  
Cell Cycle ◽  
Cyclin E ◽  
Cell Cycle Control ◽  
Terminal Differentiation ◽  
Loss Of Function ◽  
Cell Fates ◽  
Vulval Development ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Specific Number

We have identified strong loss-of-function mutations in the C. elegans cyclin E gene, cye-1. Mutations in cye-1 lead to the underproliferation of many postembryonic blast lineages as well as defects in fertility and gut-cell endoreduplication. In addition, cye-1 is required maternally, but not zygotically for embryonic development. Our analysis of vulval development in cye-1 mutants suggests that a timing mechanism may control the onset of vulval cell terminal differentiation: once induced, these cells appear to differentiate after a set amount of time, rather than a specific number of division cycles. cye-1 mutants also show an increase in the percentage of vulval precursor cells (VPCs) that adopt vulval cell fates, indicating that cell-cycle length can play a role in the proper patterning of vulval cells. By analyzing cul-1 mutants, we further demonstrate that vulval cell terminal differentiation can be uncoupled from associated changes in vulval cell division planes.

scholarly journals Visualizing the metazoan proliferation-terminal differentiation decision in vivo

2019 ◽  
Author(s):  
Rebecca C. Adikes ◽  
Abraham Q. Kohrman ◽  
Michael A. Q. Martinez ◽  
Nicholas J. Palmisano ◽  
Jayson J. Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Cell Lineage ◽  
Terminal Differentiation ◽  
Cyclin Dependent Kinase ◽  
C Elegans ◽  
Differentiated Cells ◽  
Imaging Tool ◽  
Wide Range

SummaryCell proliferation and terminal differentiation are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these cell cycle-associated events live in C. elegans and zebrafish. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from terminally differentiated cells in G0, revealing a commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. We also derive a predictive model of future proliferation behavior in C. elegans and zebrafish based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell cycle control in a wide-range of developmental contexts.

The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 181-190 ◽  
Author(s):  
J.N. Maloof ◽  
C. Kenyon
Keyword(s):  
Body Region ◽  
Ras Signaling ◽  
Cell Fates ◽  
Vulval Development ◽  
Ras Pathway ◽  
Hox Gene ◽  
C Elegans ◽  
Cell Divisions ◽  
Ras Activation ◽  
Vulval Precursor Cells

The Ras signaling pathway specifies a variety of cell fates in many organisms. However, little is known about the genes that function downstream of the conserved signaling cassette, or what imparts the specificity necessary to cause Ras activation to trigger different responses in different tissues. In C. elegans, activation of the Ras pathway induces cells in the central body region to generate the vulva. Vulval induction takes place in the domain of the Hox gene lin-39. We have found that lin-39 is absolutely required for Ras signaling to induce vulval development. During vulval induction, the Ras pathway, together with basal lin-39 activity, up-regulates lin-39 expression in vulval precursor cells. We find that if lin-39 function is absent at this time, no vulval cell divisions occur. Furthermore, if lin-39 is replaced with the posterior Hox gene mab-5, then posterior structures are induced instead of a vulva. Our findings suggest that in addition to permitting vulval cell divisions to occur, lin-39 is also required to specify the outcome of Ras signaling by selectively activating vulva-specific genes.

scholarly journals Cell cycle control of NOTCH signalling during C. elegans vulval development

2011 ◽  
Vol 356 (1) ◽  
pp. 186
Author(s):  
Stephanie Nusser-Stein ◽  
Magdalene Adamczyk ◽  
Antje Beyer ◽  
Ivo Rimann ◽  
Nir Piterman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Notch Signalling ◽  
Vulval Development ◽  
C Elegans

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.

scholarly journals Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity

2020 ◽  
Vol 21 (20) ◽  
pp. 7610 ◽  
Author(s):  
Tam Duong ◽  
Neal R. Rasmussen ◽  
David J. Reiner
Keyword(s):  
Birth Defects ◽  
Dual Function ◽  
Wild Type ◽  
Cell Fates ◽  
Vulval Development ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Anchor Cell ◽  
The Impact ◽  
Wild Type Control

The C. elegans vulva is an excellent model for the study of developmental biology and cell–cell signaling. The developmental induction of vulval precursor cells (VPCs) to assume the 3°-3°-2°-1°-2°-3° patterning of cell fates occurs with 99.8% accuracy. During C. elegans vulval development, an EGF signal from the anchor cell initiates the activation of RasLET-60 > RafLIN-45 > MEKMEK-2 > ERKMPK-1 signaling cascade to induce the 1° cell. The presumptive 1° cell signals its two neighboring cells via NotchLIN-12 to develop 2° cells. In addition, RasLET-60 switches effectors to RalGEFRGL-1 > RalRAL-1 to promote 2° fate. Shin et al. (2019) showed that RalGEFRGL-1 is a dual-function protein in VPCs fate patterning. RalGEFRGL-1 functions as a scaffold for PDKPDK-1 > AktAKT-1/2 modulatory signaling to promote 1° fate in addition to propagating the RasLET-60 modulatory signal through RalRAL-1 to promote 2° fate. The deletion of RalGEFRGL-1 increases the frequency of VPC patterning errors 15-fold compared to the wild-type control. We speculate that RalGEFRGL-1 represents an “insulated switch”, whereby the promotion of one signaling activity curtails the promotion of the opposing activity. This property might increase the impact of the switch on fidelity more than two separately encoded proteins could. Understanding how developmental fidelity is controlled will help us to better understand the origins of cancer and birth defects, which occur in part due to the misspecification of cell fates.

The evolution of cell lineage in nematodes

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 85-95
Author(s):  
Ralf J. Sommer ◽  
Lynn K. Carta ◽  
Paul W. Sternberg
Keyword(s):  
Cell Lineage ◽  
Experimental System ◽  
Nematode Species ◽  
Cell Fates ◽  
Equivalence Group ◽  
Vulval Development ◽  
C Elegans ◽  
Somatic Gonad ◽  
Vulval Precursor Cell ◽  
P Cells

The invariant development of free-living nematodes combined with the extensive knowledge of Caenorhabditis elegans developmental biology provides an experimental system for an analysis of the evolution of developmental mechanisms. We have collected a number of new nematode species from soil samples. Most are easily cultured and their development can be analyzed at the level of individual cells using techniques standard to Caenorhabditis. So far, we have focused on differences in the development of the vulva among species of the families Rhabditidae and Panagrolaimidae. Preceding vulval development, twelve Pn cells migrate into the ventral cord and divide to produce posterior daughters [Pn.p cells] whose fates vary in a position specific manner [from P1.p anterior to P12.p posterior]. In C. elegans hermaphrodites, P(3-8).p are tripotent and form an equivalence group. These cells can express either of two vulval fates (1° or 2°) in response to a signal from the anchor cell of the somatic gonad, or a non-vulval fate (3°), resulting in a 3°-3°-2°-1°-2°-3° pattern of cell fates. Evolutionary differences in vulval development include the number of cells in the vulval equivalence group, the number of 1° cells, the number of progeny generated by each vulval precursor cell, and the position of VPCs before morphogenesis. Examples of three Rhabditidae genera have a posterior vulva in the position of P9-P11 ectoblasts. In Cruznema tripartitum, P(5-7).p form the vulva as in Caenorhabditis, but they migrate posteriorly before dividing. Induction occurs after the gonad grows posteriorly to the position of P(5-7).p cells. In two other species, Mesorhabditis sp. PS 1179 and Teratorhabditis palmarum, we have found changes in induction and competence with respect to their presumably more C. elegans-like ancestor. In Mesorhabditis, P(5-7).p form the vulva after migrating to a posterior position. However, the gonad is not required to specify the pattern of cell fates 3°-2°-1°-2°-3°. Moreover, the Pn.p cells are not equivalent in their potentials to form the vulva. A regulatory constraint in this family thus forces the same set of precursors to generate the vulva, rather than more appropriately positioned Pn.p cells.

Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 231-240 ◽  
Author(s):  
E.J. Lambie ◽  
J. Kimble
Keyword(s):  
Gene Expression ◽  
Double Mutant ◽  
Transmembrane Proteins ◽  
Cell Interactions ◽  
Loss Of Function ◽  
Cell Fates ◽  
Single Mutant ◽  
C Elegans ◽  
Homologous Genes ◽  
Mutant Phenotypes

Two homologous genes, lin-12 and glp-1, encode transmembrane proteins required for regulatory cell interactions during C. elegans development. Based on their single mutant phenotypes, each gene has been thought to govern a distinct set of cell fates. We show here that lin-12 and glp-1 are functionally redundant during embryogenesis: Unlike either single mutant, the lin-12 glp-1 double mutant dies soon after hatching. Numerous cellular defects can be observed in these Lag (for lin-12 and glp-1) double mutants. Furthermore, we have identified two genes, lag-1 and lag-2, that appear to be required for both lin-12 and glp-1-mediated cell interactions. Strong loss-of-function lag mutants are phenotypically indistinguishable from the lin-12 glp-1 double; weak lag mutants have phenotypes typical of lin-12 and glp-1 single mutants. We speculate that the lin-12 and glp-1 proteins are biochemically interchangeable and that their divergent roles in development may rely largely on differences in gene expression.

scholarly journals Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2223-2234 ◽  
Author(s):  
P. M. Fox ◽  
V. E. Vought ◽  
M. Hanazawa ◽  
M.-H. Lee ◽  
E. M. Maine ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
C Elegans ◽  
Proliferative Cell

scholarly journals Control of Vulval Cell Division Number in the Nematode Oscheius/Dolichorhabditis sp. CEW1

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 183-197 ◽  
Author(s):  
Marie-Laure Dichtel ◽  
Sophie Louvet-Vallée ◽  
Mark E Viney ◽  
Marie-Anne Félix ◽  
Paul W Sternberg
Keyword(s):  
Cell Cycle ◽  
Precursor Cell ◽  
Spatial Patterning ◽  
Cell Fates ◽  
C Elegans ◽  
Induction Mechanism ◽  
Independent Mechanism ◽  
Genetic Mechanisms ◽  
Vulval Precursor Cell ◽  
Division Number

Abstract Spatial patterning of vulval precursor cell fates is achieved through a different two-stage induction mechanism in the nematode Oscheius/Dolichorhabditis sp. CEW1 compared with Caenorhabditis elegans. We therefore performed a genetic screen for vulva mutants in Oscheius sp. CEW1. Most mutants display phenotypes unknown in C. elegans. Here we present the largest mutant category, which affects division number of the vulva precursors P(4-8).p without changing their fate. Among these mutations, some reduce the number of divisions of P4.p and P8.p specifically. Two mutants omit the second cell cycle of all vulval lineages. A large subset of mutants undergo additional rounds of vulval divisions. We also found precocious and retarded heterochronic mutants. Whereas the C. elegans vulval lineage mutants can be interpreted as overall (homeotic) changes in precursor cell fates with concomitant cell cycle changes, the mutants described in Oscheius sp. CEW1 do not affect overall precursor fate and thereby dissociate the genetic mechanisms controlling vulval cell cycle and fate. Laser ablation experiments in these mutants reveal that the two first vulval divisions in Oscheius sp. CEW1 appear to be redundantly controlled by a gonad-independent mechanism and by a gonadal signal that operates partially independently of vulval fate induction.

scholarly journals Reciprocal EGFR signaling in the Anchor Cell ensures precise inter-organ connection during C. elegans vulval morphogenesis

2021 ◽  
Author(s):  
Silvan Spiri ◽  
Simon Berger ◽  
Louisa Mereu ◽  
Andrew DeMello ◽  
Alex Hajnal
Keyword(s):  
Egf Receptor ◽  
Adherens Junctions ◽  
Egfr Signaling ◽  
Cell Fates ◽  
Vulval Development ◽  
C Elegans ◽  
Sequence Of Events ◽  
Epidermal Growth ◽  
Short And Long Term ◽  
Anchor Cell

During C. elegans vulval development, the uterine anchor cell (AC) first secretes an epidermal growth factor (EGF) to specify the vulval cell fates and then invades into the underlying vulval epithelium. Thereby, the AC establishes direct contact with the invaginating primary vulF cells and attaches the developing uterus to the vulva. The signals involved and the exact sequence of events joining these two organs are not fully understood. Using a conditional let-23 egf receptor (EGFR) allele along with novel microfluidic short- and long-term imaging methods, we discovered a specific function of the EGFR in the AC during vulval lumen morphogenesis. Tissue-specific inactivation of let-23 in the AC resulted in imprecise alignment of the AC with the primary vulval cells, delayed AC invasion and disorganized adherens junctions at the newly forming contact site between the AC and the dorsal vulF toroid. We propose that EGFR signaling, activated by a reciprocal EGF cue from the primary vulval cells, positions the AC at the vulval midline, guides it during invasion and assembles a cytoskeletal scaffold organizing the adherens junctions that connect the developing uterus to the dorsal vulF toroid. EGFR signaling in the AC thus ensures the precise alignment of the two developing organs.

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