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

Grimbert, Stéphanie; Tietze, Kyria; Barkoulas, Michalis; Sternberg, Paul W.; Félix, Marie‐Anne; Braendle, Christian

doi:10.1016/j.ydbio.2016.05.036

Cited by 17 publications

(25 citation statements)

References 62 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cytoplasmic extensions can also be biased to break the symmetry of ERK activity in a field of responding cells (Peng et al, 2012). Generally, dynamic morphology of inducing cells, such as protrusive structures carrying ligand, and of responding cells, as observed in the VPC system (Grimbert et al, 2016;Huelsz-Prince and van Zon, 2017), may serve as an important control mechanism of the absolute numbers of ligand-receptor complexes formed.…”

Section: Discussionmentioning

confidence: 99%

Outstanding questions in developmental ERK signaling

Patel

Shvartsman

2018

Development

View full text Add to dashboard Cite

The extracellular signal-regulated kinase (ERK) pathway leads to activation of the effector molecule ERK, which controls downstream responses by phosphorylating a variety of substrates, including transcription factors. Crucial insights into the regulation and function of this pathway came from studying embryos in which specific phenotypes arise from aberrant ERK activation. Despite decades of research, several important questions remain to be addressed for deeper understanding of this highly conserved signaling system and its function. Answering these questions will require quantifying the first steps of pathway activation, elucidating the mechanisms of transcriptional interpretation and measuring the quantitative limits of ERK signaling within which the system must operate to avoid developmental defects.

show abstract

Section: Discussionmentioning

confidence: 99%

Outstanding questions in developmental ERK signaling

Patel

Shvartsman

2018

Development

View full text Add to dashboard Cite

show abstract

“…6). The latter is much more 543 evident in O. tipulae than in C. elegans (Grimbert et al 2016). Table S1.…”

Section: Ppa-lin-44 Cannot Represent the Vulva Induction Signal As Prmentioning

confidence: 97%

“…Concerning lin-2, lin-7 or lin-10, we now know that the proteins LIN-2/CASK, LIN- In C. elegans, vulva precursor cells are attracted towards the anchor cell in response 462 to LIN-3 signaling, thus creating a positive feedback whereby the most induced cell moves 463 closest to the anchor cell (Grimbert et al 2016). The same feedback may be at stake for the 464 2° cells, but curiously, we never observed an excess of 1°-fated cells in O. tipulae.…”

Section: The Wnt Pathway Plays a Role In Vulva Precursor Competence/imentioning

confidence: 99%

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

Félix

Velazquez

Besnard

2018

Preprint

Self Cite

View full text Add to dashboard Cite

100-word summary 49Genetic screens in the nematode Caenorhabditis elegans identified EGF and Notch pathways 50 as key for vulval precursor cell fate patterning. Here we report on the molecular identification 51 of mutations affecting vulval induction in another nematode, Oscheius tipulae. The single 52 mutation with reduced induction is identified as a cis-regulatory deletion in the O. tipulae lin-3 53 homolog, confirmed by CRISPR/Cas9 mutation. In contrast to this predictable Vulvaless 54 mutation, mutations resulting in an excess of 2° vulval fates unexpectedly correspond to the 55 plexin/semaphorin pathway, not implicated in vulval induction in C. elegans. This study 56 highlights both necessity and contingency in forward genetic screens.

show abstract

“…Besides VPC fate specification, LIN-3 to LET-23 signaling is also required for the proper alignment 283 between the AC and the 1° VPC P6.p (Grimbert et al, 2016). In wild-type L2 stage larvae, the relative 284 position between the AC and VPCs is highly variable.…”

Section: Chp-1 Is Necessary For the Precise Ac To P6p Alignment 282mentioning

confidence: 99%

The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling inC. elegansand in human cells

Haag

Walser

Henggeler

et al. 2019

Preprint

View full text Add to dashboard Cite

14The intracellular trafficking of growth factor receptors determines the activity of their 15 downstream signaling pathways. The putative co-chaperone CHP-1 acts as a regulator of EGFR 16 trafficking during C.elegans vulval development. Loss of chp-1 causes the retention of the 17 EGFR in the ER and decreased MAPK signaling. CHP-1 functions specifically, as the localization 18 of other receptors is unaltered in chp-1(lf) mutants, and inhibiting other co-chaperones does 19 not affect EGFR localization. The role of CHP-1 during EGFR trafficking is conserved in 20 humans. Analogous to C.elegans, the response of CHP-1-deficient human cells to EGF 21 stimulation is attenuated, the EGFR accumulates in the ER and ERK2 activity is decreased. 22Although CHP-1 has been proposed to act as a co-chaperone for HSP90, our data indicate an 23 HSP90-independent function of CHP-1. The identification of CHP-1 as a regulator of EGFR24 trafficking opens the possibility to identify small molecule chaperone inhibitors targeting the 25 EGFR pathway with increased selectivity. 26 Thanks to the availability of functional GFP tagged LET-23 reporters and the transparent body, vulval 55 development is an excellent model to observe EGFR trafficking and localization in the epithelial VPCs 56 of living animals (Haag et al, 2014). Before vulval induction, LET-23 is equally expressed in all VPCs. 57 During induction, a positive MAP kinase MPK-1 feedback signal up-regulates LET-23 expression in 58 P6.p, which allows this cell to sequester most of the inductive LIN-3 EGF signal (Stetak et al, 2006). 59 By contrast, LIN-12 NOTCH signaling in P5.p and P7.p results in the down-regulation of LET-23 and 60 Haag et al. 4 the inhibition of RAS/MAPK signaling (Whitfield et al, 1999). 61 Several factors that regulate RAS/MAPK activity by controlling the sub-cellular localization and 62 trafficking of the LET-23 EGFR in the VPCs have been identified. The basolateral localization of LET-63 23 by the tripartite LIN-2/CASK, LIN-10/ MINT and LIN-7/VELIS protein complex is necessary for 64 efficient receptor activation, because LIN-3 is secreted by the AC in the somatic gonad facing the 65 basolateral compartment of the VPCs (Kaech et al, 1998;Hoskins et al, 1996). On the other hand, the 66 ARF GTPase exchange factor AGEF-1 antagonizes via the ARF GTPase and the AP-1 adaptor complex 67 the basolateral localization of LET-23 (Skorobogata et al, 2014). A systematic in vivo screen in live C. 68 elegans larvae has identified multiple additional regulators of LET-23 localization and signaling 69 (Haag et al, 2014). One candidate identified in this screen was chp-1, which encodes a Cysteine and 70Histidine Rich Domain (CHORD) containing protein homologous to human CHORDC1 (also named 71Morgana) (Brancaccio et al, 2003;Ferretti et al, 2011). CHORDC1 has been proposed to function as 72 co-chaperone with HSP90, though CHORDC1 may also act independently of HPS90 (Gano & Simon, 73 2010a). 74Here, we show that a loss of chp-1 function in C. elegans leads to the accumulat...

show abstract

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

Cited by 17 publications

References 62 publications

Outstanding questions in developmental ERK signaling

Outstanding questions in developmental ERK signaling

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

The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling inC. elegansand in human cells

Contact Info

Product

Resources

About