scholarly journals The Signaling Network Controlling C. elegans Vulval Cell Fate Patterning

2018 ◽  
Vol 6 (4) ◽  
pp. 30 ◽  
Author(s):  
Hanna Shin ◽  
David Reiner
Keyword(s):  
Cell Fate ◽  
Signaling Network ◽  
Signaling Cascades ◽  
Cell Fates ◽  
C Elegans ◽  
Differentiated Cells ◽  
Vulval Precursor Cells ◽  
Cell Patterns ◽  
History Of ◽  
Anchor Cell

EGF, emitted by the Anchor Cell, patterns six equipotent C. elegans vulval precursor cells to assume a precise array of three cell fates with high fidelity. A group of core and modulatory signaling cascades forms a signaling network that demonstrates plasticity during the transition from naïve to terminally differentiated cells. In this review, we summarize the history of classical developmental manipulations and molecular genetics experiments that led to our understanding of the signals governing this process, and discuss principles of signal transduction and developmental biology that have emerged from these studies.

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.

scholarly journals Morphogenesis of the C. elegans hermaphrodite uterus

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3617-3626 ◽  
Author(s):  
A.P. Newman ◽  
J.G. White ◽  
P.W. Sternberg
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Cell Types ◽  
Cell Interaction ◽  
Cell Fate Decision ◽  
Cell Fates ◽  
C Elegans ◽  
A Cell ◽  
Anchor Cell ◽  
Fate Decision

We have undertaken electron micrographic reconstruction of the Caenorhabditis elegans hermaphrodite uterus and determined the correspondence between cells defined by their lineage history and differentiated cell types. In this organ, many cells do not move during morphogenesis and the cell lineage may function to put cells where they are needed. Differentiated uterine cell types include the toroidal ut cells that make structural epithelium, and specialized utse and uv cells that make the connection between the uterus and the vulva. A cell fate decision in which the anchor cell (AC) induces adjacent ventral uterine intermediate precursor cells to adopt the pi fate, rather than the ground state rho, has profound consequences for terminal differentiation: all pi progeny are directly involved in making the uterine-vulval connection whereas all rho progeny contribute to ut toroids or the uterine-spermathecal valve. In addition to specifying certain uterine cell fates, the AC also induces the vulva. Its multiple inductions thereby function to coordinate the connection of an internal to an external epithelium. The AC induces the pi cells and ultimately fuses with a subset of their progeny. This is an example of reciprocal cell-cell interaction that can be studied at single cell resolution. The AC is thus a transitory cell type that plays a pivotal role in organizing the morphogenesis of the uterine-vulval connection.

The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3615-3626 ◽  
Author(s):  
K.L. Chow ◽  
D.H. Hall ◽  
S.W. Emmons
Keyword(s):  
Cell Fate ◽  
Hox Genes ◽  
Cell Signalling ◽  
Gene Mutations ◽  
Genetic Modifiers ◽  
Tail Region ◽  
Cell Fates ◽  
C Elegans ◽  
Body Regions ◽  
Novel Protein

The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-to-anterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOM-C/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.

Patterning of the C. elegans 1 degrees vulval lineage by RAS and Wnt pathways

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5047-5058 ◽  
Author(s):  
M. Wang ◽  
P.W. Sternberg
Keyword(s):  
Short Range ◽  
Precursor Cell ◽  
Ras Signaling ◽  
Cell Fates ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Anchor Cell ◽  
Wnt Pathways ◽  
Vulval Precursor Cell ◽  
Proper Orientation

In C. elegans, the descendants of the 1 degrees vulval precursor cell (VPC) establish a fixed spatial pattern of two different cell fates: E-F-F-E. The two inner granddaughters attach to the somatic gonadal anchor cell (AC) and generate four vulF cells, while the two outer granddaughters produce four vulE progeny. zmp-1::GFP, a molecular marker that distinguishes these two fates, is expressed in vulE cells, but not vulF cells. We demonstrate that a short-range AC signal is required to ensure that the pattern of vulE and vulF fates is properly established. In addition, signaling between the inner and outer 1 degrees VPC descendants, as well as intrinsic polarity of the 1 degrees VPC daughters, is involved in the asymmetric divisions of the 1 degrees VPC daughters and the proper orientation of the outcome. Finally, we provide evidence that RAS signaling is used during this new AC signaling event, while the Wnt receptor LIN-17 appears to mediate signaling between the inner and outer 1 degrees VPC descendants.

Comparative developmental studies using Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae)

Nematology ◽  
2000 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Marie Delattre ◽  
Marie-Laure Dichtel ◽  
Marie-Anne Félix
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Precursor Cells ◽  
Developmental Studies ◽  
Morphological Markers ◽  
Molecular Tools ◽  
Ras Gene ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Anchor Cell

AbstractIn order to study the evolution of nematode vulva development, we focus on Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) in comparison with Caenorhabditis elegans. In this species, the fates of the vulval precursor cells are determined by two successive nested inductions by the uterine anchor cell (instead of a single one in C. elegans). This hermaphroditic species can be cultured and handled like C. elegans. We review vulva development in this species. We present some molecular tools and the sequence of the Ras gene. This species is amenable to genetic analysis and we discuss the isolation of morphological markers. Afin d’étudier l’évolution du développement de la vulve des nématodes, nous nous concentrons sur l’espèce Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) en la comparant à Caenorhabditis elegans. Dans cette espèce, les destinées des cellules précurseurs de la vulve sont déterminées par deux inductions emboîtées provenant de la cellule ancre de l’utérus (au lieu d’une seule chez C. elegans). Cette espèce hermaphrodite peut être élévée et manipulée comme C. elegans. Nous décrivons le développement de la vulve dans cette espèce. Nous présentons des outils moléculaires et la séquence du gène Ras. Les analyses génétiques sont possibles dans cette espèce et nous discutons l’isolement de marqueurs morphologiques.

scholarly journals PAG-3, a Zn-finger transcription factor, determines neuroblast fate in C. elegans

Development ◽  
2002 ◽  
Vol 129 (7) ◽  
pp. 1763-1774 ◽  
Author(s):  
Scott Cameron ◽  
Scott G. Clark ◽  
Joan B. McDermott ◽  
Eric Aamodt ◽  
H. Robert Horvitz
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Daughter Cell ◽  
Cell Lineage ◽  
Blast Cell ◽  
Cell Fates ◽  
Zinc Finger Transcription Factor ◽  
C Elegans ◽  
Mother Cells

During Caenorhabditis elegans development, the patterns of cell divisions, cell fates and programmed cell deaths are reproducible from animal to animal. In a search for mutants with abnormal patterns of programmed cell deaths in the ventral nerve cord, we identified mutations in the gene pag-3, which encodes a zinc-finger transcription factor similar to the mammalian Gfi-1 and Drosophila Senseless proteins. In pag-3 mutants, specific neuroblasts express the pattern of divisions normally associated with their mother cells, producing with each reiteration an abnormal anterior daughter neuroblast and an extra posterior daughter cell that either terminally differentiates or undergoes programmed cell death, which accounts for the extra cell corpses seen in pag-3 mutants. In addition, some neurons do not adopt their normal fates in pag-3 mutants. The phenotype of pag-3 mutants and the expression pattern of the PAG-3 protein suggest that in some lineages pag-3 couples the determination of neuroblast cell fate to subsequent neuronal differentiation. We propose that pag-3 counterparts in other organisms determine blast cell identity and for this reason may lead to cell lineage defects and cell proliferation when mutated.

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.

scholarly journals A developmental gene regulatory network for invasive differentiation of theC. elegansanchor cell

2019 ◽  
Author(s):  
Taylor N. Medwig-Kinney ◽  
Jayson J. Smith ◽  
Nicholas J. Palmisano ◽  
Sujata Tank ◽  
Wan Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
Cell Biology ◽  
Type I ◽  
Cell Specification ◽  
C Elegans ◽  
Gene Regulatory ◽  
Anchor Cell

ABSTRACTCellular invasion is a key part of development, immunity, and disease. Using thein vivomodel ofC. elegansanchor cell invasion, we characterize the gene regulatory network that promotes invasive differentiation. The anchor cell is initially specified in a stochastic cell fate decision mediated by Notch signaling. Previous research has identified four conserved transcription factors,fos-1a(Fos),egl-43(EVI1/MEL),hlh-2(E/Daughterless) andnhr-67(NR2E1/TLX), that mediate anchor cell specification and/or invasive differentiation. Connections between these transcription factors and the underlying cell biology that they regulate is poorly understood. Here, using genome editing and RNA interference, we examine transcription factor interactions prior to and after anchor cell specification. During invasion we identify thategl-43,hlh-2, andnhr-67function together in a type I coherent feed-forward loop with positive feedback. Conversely, prior to specification, these transcription factors function independent of one another to regulate LIN-12 (Notch) activity. Together, these results demonstrate that, although the same transcription factors can function in fate specification and differentiated cell behavior, a gene regulatory network can be rapidly re-wired to reinforce a post-mitotic, pro-invasive state.SUMMARY STATEMENTBasement membrane invasion by theC. elegansanchor cell is coordinated by a dynamic gene regulatory network encompassing cell cycle dependent and independent sub-circuits.

scholarly journals The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5277-5284 ◽  
Author(s):  
T. von Zelewsky ◽  
F. Palladino ◽  
K. Brunschwig ◽  
H. Tobler ◽  
A. Hajnal ◽  
...  
Keyword(s):  
Cell Fate ◽  
Central Component ◽  
Cell Fate Determination ◽  
Nurd Complex ◽  
Fate Determination ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
The Subject ◽  
Biochemical Analyses ◽  
Ras Signalling

The Mi-2 protein is the central component of the recently isolated NuRD nucleosome remodelling and histone deacetylase complex. Although the NuRD complex has been the subject of extensive biochemical analyses, little is known about its biological function. Here we show that the two C. elegans Mi-2 homologues, LET-418 and CHD-3, play essential roles during development. The two proteins possess both shared and unique functions during vulval cell fate determination, including antagonism of the Ras signalling pathway required for vulval cell fate induction and the proper execution of the 2 degrees cell fate of vulval precursor cells, a process under the control of LIN-12 Notch signalling.

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