Faculty Opinions recommendation of Anchor cell signaling and vulval precursor cell positioning establish a reproducible spatial context during C. elegans vulval induction.

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.

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Necessity and contingency in developmental genetic screens: LIN-3, Wnt and semaphorin pathways in vulval induction of the nematode Oscheius tipulae

10.1101/383729 ◽

2018 ◽

Cited By ~ 1

Author(s):

Amhed M. Vargas-Velazquez ◽

Fabrice Besnard ◽

Marie-Anne Félix

Keyword(s):

Caenorhabditis Elegans ◽

Cell Fate ◽

Wnt Pathway ◽

Precursor Cell ◽

Genetic Screens ◽

C Elegans ◽

Forward Genetic Screens ◽

Anchor Cell ◽

Notch Pathways ◽

Vulval Precursor Cell

AbstractGenetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. Schematically, the anchor cell secretes EGF, inducing the P6.p cell to a 1° vulval fate; P6.p in turn induces its neighbors to a 2° fate through Delta-Notch signaling and represses Ras signaling. In the nematode Oscheius tipulae, the anchor cell successively induces 2° then 1° vulval fates. Here we report on the molecular identification of mutations affecting vulval induction in O. tipulae. A single Induction Vulvaless mutation was found, which we identify as a cis-regulatory deletion in a tissue-specific enhancer of the O. tipulae lin-3 homolog, confirmed by CRISPR/Cas9 mutation. In contrast to this predictable Vulvaless mutation, mutations resulting in an excess of 2° fates unexpectedly correspond to the plexin/semaphorin pathway, which was not implicated in vulval fate induction in C. elegans. Hyperinduction of P4.p and P8.p in these mutants likely results from mispositioning of these cells due to a lack of contact inhibition. The third signaling pathway found by forward genetics in O. tipulae is the Wnt pathway: decrease in Wnt pathway activity results in loss of vulval precursor competence and induction, and 1° fate miscentering on P5.p. Our results suggest that the EGF and Wnt pathways have qualitatively similar activities in vulval induction in C. elegans and O. tipulae, albeit with quantitative differences in the effects of mutation. This study highlights both necessity and contingency in forward genetic screens.100-word summaryGenetic screens in the nematode Caenorhabditis elegans identified EGF and Notch pathways as key for vulval precursor cell fate patterning. Here we report on the molecular identification of mutations affecting vulval induction in another nematode, Oscheius tipulae. The single mutation with reduced induction is identified as a cis-regulatory deletion in the O. tipulae lin-3 homolog, confirmed by CRISPR/Cas9 mutation. In contrast to this predictable Vulvaless mutation, mutations resulting in an excess of 2° vulval fates unexpectedly correspond to the plexin/semaphorin pathway, not implicated in vulval induction in C. elegans. This study highlights both necessity and contingency in forward genetic screens.

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

Genetics ◽

10.1093/genetics/157.1.183 ◽

2001 ◽

Vol 157 (1) ◽

pp. 183-197 ◽

Cited By ~ 1

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.

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The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development

Development ◽

10.1242/dev.125.18.3667 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3667-3680 ◽

Cited By ~ 39

Author(s):

D.M. Eisenmann ◽

J.N. Maloof ◽

J.S. Simske ◽

C. Kenyon ◽

S.K. Kim

Keyword(s):

Signaling Pathway ◽

Cell Fate ◽

Precursor Cell ◽

Ras Signaling ◽

Beta Catenin ◽

Cell Fates ◽

Vulval Development ◽

Hox Gene ◽

C Elegans ◽

Vulval Precursor Cell

In C. elegans, the epithelial Pn.p cells adopt either a vulval precursor cell fate or fuse with the surrounding hypodermis (the F fate). Our results suggest that a Wnt signal transduced through a pathway involving the beta-catenin homolog BAR-1 controls whether P3.p through P8.p adopt the vulval precursor cell fate. In bar-1 mutants, P3.p through P8.p can adopt F fates instead of vulval precursor cell fates. The Wnt/bar-1 signaling pathway acts by regulating the expression of the Hox gene lin-39, since bar-1 is required for LIN-39 expression and forced lin-39 expression rescues the bar-1 mutant phenotype. LIN-39 activity is also regulated by the anchor cell signal/let-23 receptor tyrosine kinase/let-60 Ras signaling pathway. Our genetic and molecular experiments show that the vulval precursor cells can integrate the input from the BAR-1 and LET-60 Ras signaling pathways by coordinately regulating activity of the common target LIN-39 Hox.

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Semaphorin 1a and semaphorin 1b are required for correct epidermal cell positioning and adhesion during morphogenesis in C. elegans

Development ◽

10.1242/dev.129.9.2065 ◽

2002 ◽

Vol 129 (9) ◽

pp. 2065-2078

Author(s):

Val E. Ginzburg ◽

Peter J. Roy ◽

Joseph G. Culotti

Keyword(s):

Axon Guidance ◽

Transmembrane Proteins ◽

Precursor Cell ◽

Deletion Mutants ◽

Normal Position ◽

C Elegans ◽

Seam Cell ◽

Ray Cells ◽

Cell Positioning ◽

Anterior Posterior

The semaphorin family comprises secreted and transmembrane proteins involved in axon guidance and cell migration. We have isolated and characterized deletion mutants of C. elegans semaphorin 1a (Ce-sema-1a or smp-1) and semaphorin 1b (Ce-sema-1b or smp-2) genes. Both mutants exhibit defects in epidermal functions. For example, the R1.a-derived ray precursor cells frequently fail to change anterior/posterior positions completely relative to their sister tail lateral epidermal precursor cell R1.p, causing ray 1 to be formed anterior to its normal position next to ray 2. The ray cells, which normally separate from the lateral tail seam cell (SET) at the end of L4 stage, remains connected to the SET cell even in adult mutant males. The ray 1 defects are partially penetrant in each single Ce-sema-1 mutant at 20°C, but are greatly enhanced in Ce-sema-1 double mutants, suggesting that Ce-Sema-1a and Ce-Sema-1b function in parallel to regulate ray 1 position. Both mutants also have defects in other aspects of epidermal functions, including head and tail epidermal morphogenesis and touch cell axon migration, whereas, smp-1 mutants alone have defects in defecation and brood size. A feature of smp-1 mutants that is shared with mutants of mab-20 (which encodes Sema-2a) is the abnormal perdurance of contacts between epidermal cells.

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LIN-12 protein expression and localization during vulval development in C. elegans

Development ◽

10.1242/dev.125.16.3101 ◽

1998 ◽

Vol 125 (16) ◽

pp. 3101-3109 ◽

Cited By ~ 5

Author(s):

D. Levitan ◽

I. Greenwald

Keyword(s):

Cell Fate ◽

Feedback Mechanism ◽

Precursor Cell ◽

Vulval Development ◽

Ras Pathway ◽

Cell Fate Decisions ◽

C Elegans ◽

Somatic Gonad ◽

Multiple Cell ◽

Vulval Precursor Cell

We have used a LIN-12::GFP fusion protein to examine LIN-12 accumulation during cell fate decisions important for vulval development. During the naturally variable anchor cell (AC)/ventral uterine precursor cell (VU) decision of the somatic gonad, a transcription-based feedback mechanism biases two equivalent cells so that one becomes the AC while the other becomes a VU. LIN-12::GFP accumulation reflects lin-12 transcription: LIN-12::GFP is initially present in both cells, but disappears from the presumptive AC and becomes restricted to the presumptive VU. During vulval precursor cell (VPC) fate determination, six equipotential cells uniformly transcribe lin-12 and have invariant fates that are specified by multiple cell-cell interactions. The pattern of LIN-12::GFP accumulation in VPCs and in the VPC lineages is dynamic and does not always reflect lin-12 transcription. In particular, LIN-12::GFP is expressed initially in all six VPCs, but appears to be reduced specifically in P6.p as a consequence of the activation of the Ras pathway by an EGF-like inductive signal from the AC. We propose that downregulation of LIN-12 stability or translation in response to inductive signalling helps impose a bias on lateral signalling and contributes to the invariant pattern of VPC fates.

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