scholarly journals Integration of EGFR and LIN-12/Notch Signaling by LIN-1/Elk1, the Cdk8 Kinase Module, and SUR-2/Med23 in Vulval Precursor Cell Fate Patterning in  Caenorhabditis elegans

Genetics ◽  
2017 ◽  
pp. genetics.300192.2017 ◽  
Author(s):  
Ryan Underwood ◽  
Yuting Deng ◽  
Iva Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Notch Signaling ◽  
Cell Fate ◽  
Precursor Cell ◽  
Vulval Precursor Cell

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

2018 ◽  
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.

scholarly journals Variability in β-catenin pulse dynamics in a stochastic cell fate decision in C. elegans

2018 ◽  
Author(s):  
Jason R. Kroll ◽  
Jasonas Tsiaxiras ◽  
Jeroen S. van Zon
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Fusion ◽  
Precursor Cell ◽  
Cell Fate Decision ◽  
Absolute Level ◽  
Cell Fate Decisions ◽  
Pulse Dynamics ◽  
Significant Variability ◽  
Fate Decision

AbstractDuring development, cell fate decisions are often highly stochastic, but with the frequency of the different possible fates tightly controlled. To understand how signaling networks control the cell fate frequency of such random decisions, we studied the stochastic decision of the Caenorhabditis elegans P3.p cell to either fuse to the hypodermis or assume vulva precursor cell fate. Using time-lapse microscopy to measure the single-cell dynamics of two key inhibitors of cell fusion, the Hox gene LIN-39 and Wnt signaling through the β-catenin BAR-1, we uncovered significant variability in the dynamics of LIN-39 and BAR-1 levels. Most strikingly, we observed that BAR-1 accumulated in a single, 1-4 hour pulse at the time of the P3.p cell fate decision, with strong variability both in pulse slope and time of pulse onset. We found that the time of BAR-1 pulse onset was delayed relative to the time of cell fusion in mutants with low cell fusion frequency, linking BAR-1 pulse timing to cell fate outcome. Overall, a model emerged where animal-to-animal variability in LIN-39 levels and BAR-1 pulse dynamics biases cell fate by modulating their absolute level at the time cell fusion is induced. Our results highlight that timing of cell signaling dynamics, rather than its average level or amplitude, could play an instructive role in determining cell fate.Article summaryWe studied the stochastic decision of the Caenorhabditis elegans P3.p cell to either fuse to the hypodermis or assume vulva precursor cell fate. We uncovered significant variability in the dynamics of LIN-39/Hox and BAR-1/β-catenin levels, two key inhibitors of cell fusion. Surprisingly, we observed that BAR-1 accumulated in a 1-4 hour pulse at the time of the P3.p cell fate decision, with variable pulse slope and time of pulse onset. Our work suggests a model where animal-to-animal variability in LIN-39 levels and BAR-1 pulse dynamics biases cell fate by modulating their absolute level at the time cell fusion is induced.

Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2655-2666 ◽  
Author(s):  
M. Koga ◽  
Y. Ohshima
Keyword(s):  
Caenorhabditis Elegans ◽  
Gene Function ◽  
Larval Survival ◽  
Precursor Cell ◽  
Kinase Gene ◽  
Genetic Mosaic ◽  
Tyrosine Kinase Gene ◽  
Receptor Tyrosine Kinase Gene ◽  
Almost All ◽  
Vulval Precursor Cell

The let-23 receptor tyrosine kinase gene is required for vulval induction and larval survival in the nematode Caenorhabditis elegans. We carried out genetic mosaic analyses of the let-23 gene function by using the cloned let-23 and ncl-1 genes. The wild-type let-23 gene was required in a vulval precursor cell to adopt the 1 degree vulval fate in animals carrying a let-23 vulvaless or lethal chromosomal mutation. In almost all the animals, vulval precursor cells adjacent to a 1 degree fate cell were induced to the 2 degrees vulval fate regardless of the let-23 genotypes. These findings indicate that the vulval induction signal from an anchor cell induces a vulval precursor cell to adopt the 1 degree fate through LET-23, and then a 1 degree fate cell induces adjacent cells to adopt the 2 degrees fate, for which LET-23 is not required. Foci of lethality of the let-23 (mn23) mutation were found in ABal and ABplp lineages.

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

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3667-3680 ◽  
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.

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

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3101-3109 ◽  
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.

scholarly journals LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Pengpeng Li ◽  
Kevin M Collins ◽  
Michael R Koelle ◽  
Kang Shen
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Notch Signaling ◽  
Cell Fate ◽  
Dendritic Spine ◽  
Target Selection ◽  
Ectopic Expression ◽  
Cell Types ◽  
Synaptic Connectivity ◽  
Target Cells

The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells.

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