Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis
Posted on: 9 April 2019
Preprint posted on 4 March 2019
Two independent ways tune Rho1 activity: 'Wireless' and 'non-Wireless'.
Selected by Ivana Viktorinová
Categories: cell biology, developmental biology
Rho1 signaling in the Drosophila ectoderm
Wireless/p114RhoGEF is required for the junctional Rho1 signaling (green) in order to regulate Myosin II planar polarized localization (wires-like pattern). Medio-apical Rho1 signaling is indicated in magenta. Both Rho1 signaling pathways contribute to actomyosin contractility, which in turn results in elongation of this ectodermal tissue in the Drosophila embryo (schematic visualization).
Summary and background
This preprint by Garcia De Las Bayonas et al. (the Thomas Lecuit lab, Marseille, France) aims to identify upstream regulators of Rho1 activity in germband extension during Drosophila embryogenesis. Based on their previous work and that of others, this process is driven by cell intercalation that depends on medio-apical Myosin II pulsing activity and the planar polarized vertical junctional Myosin II pool, resulting in a shrinkage of vertical junctions, cell shape changes and in subsequent Drosophila embryo elongation. How actomyosin contractility is precisely regulated upstream of the Rho1 activity remains unclear not only for this tissue, but also for other animal tissues.
Findings
- To find out where is localized the active Rho1 in the Drosophila ectoderm, the authors elegantly employed a Rho1-GFP biosensor that binds active Rho1-GTP, revealing that active Rho1 localizes medio-apically and in a polarized manner at junctions in ectodermal cells. This differs from uniform Rho1 protein distribution at cell junctions, indicating that Rho1 activity is spatially regulated. From the authors’ previous work, it is known that RhoGEF2 regulates the medio-apical pool of Myosin II. Here the authors provide further evidence that RhoGEF2 activity is polarized and regulates medio-apical Rho1 activity but not the Rho1 activity at cell junction.
- The puzzling bit comes when the authors find that the RhoGEF2 protein itself localizes apically, at cell junctions and also resembles comets in the cytoplasm of ectodermal cells. What regulates medio-apical RhoGEF2 activity to spatially activate medio-apical Rho1 signaling? Inspired by the work from the Drosophila mesoderm, the authors find that Gα12/13/Cta is required to localize RhoGEF2 and that it does so by releasing RhoGEF2 from microtubule plus ends in order to recruit it medio-apically and at cell junctions. However, it remains to be resolved what regulator restricts RhoGEF2 activity medio-apically.
- Next, the authors wanted to know what regulates the junctional Rho1 signaling. By knocking down all 26 RhoGEFs and looking at the defects of germband extension, the authors find an uncharacterized gene CG10188. It is the ortholog of mammalian p114RhoGEF and causes main germband extension defects. The authors find that its knock-down affects active Rho1 levels, Myosin II and E-cadherin specifically at cell junctions. Vice versa, p114RhoGEF overexpression increases Myosin II junctional localization and its planar polarity there. This provides evidence that actomyosin contractility at cell junctions is regulated by p114RhoGEF. As Myosin II resembles wires in the tissue and that these wires are lost upon p114RhoGEF knock-down, the authors call the p114RhoGEF gene ‘Wireless’.
- This leads the authors to a conclusion that Wireless and RhoGEF2 have additive but non-redundant function in ectodermal cells. One regulates Rho1 activity at cell junction while the other one regulates Rho1 activity medio-apically.
- So how can the Wireless protein work/regulate Rho1 activity at junctions? First, the authors investigated Wireless subcellular localization and found that Wireless-GFP exclusively localizes at cell junctions in the ectoderm. Its junctional enrichment is controlled by the G proteins Gβ13F/Gγ1, previously found to regulate medio-apical and junctional Myosin II. Together, Gβ13F/Gγ1 and p114RhoGEF/Wireless quantitatively tune Rho1 activity in order to regulate Myosin II only at cell junctions.
Conclusion
This preprints identifies two independent Rho1 signaling pathways that regulate actomyosin contractility in two different cell compartments, medio-apically and at cell junction in the Drosophila ectoderm. RhoGEF2 regulates medio-apical Rho1 activity while p114RhoGEF/Wireless controls Rho1 activity at junctions in the Drosophila ectoderm. The authors also identify that these RhoGEFs are under spatial control of distinct G protein subunits.
Placed to a bigger picture, the authors suggest that the Rho1 signaling might be evolutionarily conserved in terms of combinations of various G proteins together with RhoGEFs/RhoGAPs in other invertebrate and vertebrate systems.
Interestingly, the Wireless pathway is not present in the Drosophila mesoderm where no intercalations can be found. Therefore, it will be interesting to test whether such identified mechanism that distinguish medio-apical and junctional Rho1 pool is also applicable on the other Drosophila tissues such as male genitalia where angular cell intercalation drives tissue rotation1. On a similar note, it will be interesting to test whether a similar medio-apical RhoGEF2 pathway may work during the Myosin II pulsing phase in mid Drosophila oogenesis2.
Figure S7 of the prerpint
Why I chose it
This preprint is, as always, an inspirational piece of work from the Lecuit lab. It is a must read for scientists interested in the involvement of actomyosin contractility in developmental processes.
References
1 Sato, K. et al. Left-right asymmetric cell intercalation drives directional collective cell movement in epithelial morphogenesis. Nat Commun 6, 10074, doi:10.1038/ncomms10074 (2015).
2 He, L., Wang, X., Tang, H. L. & Montell, D. J. Tissue elongation requires oscillating contractions of a basal actomyosin network. Nat Cell Biol 12, 1133-1142, doi:10.1038/ncb2124 (2010).
Questions for the authors
- The localization of the Wireless and Gβ13F/Gγ1 proteins are not planar polarized at junctions in contrast to Rho1 and Myosin II. Have you investigated any of the 23 RhoGAP candidates that inactivate Rho1 function? Are there perhaps any candidates that are polarized at cell membranes in an opposite way, i.e. on the transverse junctions?
- Why do you think there is a need for two different Rho1 signaling pathways within ectodermal cells, would the Wireless pathway be not sufficient to drive the germband extension by itself?
doi: https://doi.org/10.1242/prelights.9773
Read preprint
(No Ratings Yet)Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Felipe Del Valle Batalla
Also in the developmental biology category:
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis
Ankita Walvekar
Actin-based deformations of the nucleus control multiciliated ependymal cell differentiation
Ryan Harrison
preLists in the cell biology category:
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
| List by | Felipe Del Valle Batalla et al. |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
| List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
| List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |
Also in the developmental biology category:
BSDB/GenSoc Spring Meeting 2024
A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.
| List by | Joyce Yu, Katherine Brown |
GfE/ DSDB meeting 2024
This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.
| List by | Joyce Yu |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
| List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
2nd Conference of the Visegrád Group Society for Developmental Biology
Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)
| List by | Nándor Lipták |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
EMBL Conference: From functional genomics to systems biology
Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020
| List by | Jesus Victorino |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
| List by | Alex Eve |
Society for Developmental Biology 79th Annual Meeting
Preprints at SDB 2020
| List by | Irepan Salvador-Martinez, Martin Estermann |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EDBC Alicante 2019
Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.
| List by | Sergio Menchero et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
| List by | Alex Eve |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Young Embryologist Network Conference 2019
Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London
| List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
| List by | Alexa Sadier |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
Zebrafish immunology
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
| List by | Shikha Nayar |