Close

Rnf20 shapes the endothelial control of heart morphogenesis and function

Linda Kessler, Rui Gao, Nalan Tetik-Elsherbiny, Olga Lityagina, Azhar Zhailauova, Yonggang Ren, Felix A. Trogisch, Julio Cordero, Yanliang Dou, Yinuo Wang, Evgeny Chichelnitskiy, Joscha Alexander Kraske, Patricia Laura Schäfer, Chi-Chung Wu, Guillermo Barreto, Michael Potente, Thomas Wieland, Roxana Ola, Joerg Heineke, Gergana Dobreva

Preprint posted on 17 September 2022 https://www.biorxiv.org/content/10.1101/2022.09.16.508288v1

Cellular Crosstalk: How Rnf20 communicates across cell types during cardiac development

Selected by Emma Armitage

Background

The heart is a complex organ which is made up of distinct cell types which carry out different functions. Crosstalk between the two main cell types of the heart – the Endocardial Cells (EC) and Cardiomyocytes (CM) – is important for correct heart development, and when prevented can lead to disease. During early heart development the heart forms a linear tube, with the endocardium making up the inner layer, while the myocardium forms the outer layer. These tissues are separated by extracellular matrix (ECM) through which they communicate via paracrine signalling. The linear heart tube grows through the addition of a population of cells known as the Second Heart Field (SHF). These cells are multipotent and can give rise to either CM or EC. Despite signalling between CM and EC being important for correct heart development, it is greatly understudied. This preprint discusses the role of a gene called Rnf20, which is essential for EC-CM crosstalk during cardiac development. The authors’ aim was to understand how EC-specific deletion of Rnf20 leads to cardiac defects. This was achieved using Cre deleter lines in mice, to delete Rnf20 in specific cell types such as Isl1+ SHF progenitor cells, and Tie2+ endocardial cells.

Key Findings

Rnf20 is required in the SHF to control ECM dynamics

This study shows that Rnf20 is an important gene controlling EC-CM crosstalk during different stages of cardiac morphogenesis. Deletion of Rnf20 in Isl1+ SHF progenitor cells resulted in cardiac defects such as a shortened outflow tract and smaller right ventricle, along with abnormal trabeculation. This is thought to be due to a reduction in expression of genes associated with ECM degradation in Rnf20 depleted Isl1+ hearts, and ECM degradation is important for correct myocardial morphogenesis. Rnf20 depleted SHF cells being unable to degrade the ECM suggests an important role for Rnf20 in the SHF to control ECM dynamics during cardiac development.

Rnf20 inhibits EndoMT in ECs to maintain endothelial identify

Next, the authors showed that Rnf20 safeguards EC identify by inhibiting endothelial to mesenchymal transition (EndMT). This is a process during which endothelial cells lose cellular features associated with endothelial cells and obtain features associated with mesenchymal cells, such as becoming more migratory and increasing secretion of ECM proteins. Rnf20 deficient EC show increased migratory capacity and an upregulation of EndMT markers, indicating that Rnf20 is required within EC to maintain their endothelial state.

Loss of Rnf20 in EC results in increased ECM deposition

Finally, the authors found that Rnf20 is required within EC to maintain physiological angiocrine signalling using a novel cell-culture based system in which endothelial cells and cardiomyocytes are co-differentiated from mouse pluripotent stem cells. Upon deletion of Rnf20 in EC this led to upregulation of ECM proteins, resulting in defects in cardiac morphology and function due to excessive ECM deposition which can alter tissue stiffness. As levels of cardiac stiffness are required to mediate CM proliferation, maturation, and contractility, this increased cardiac stiffness caused by excessive ECM deposition led to CM binucleation and irregular contractility.

Overall, this preprint demonstrates the importance of Rnf20 in EC to control numerous aspects of heart morphogenesis.

What I like this preprint/Why it is important

I chose this preprint because I am interested in understanding the complex process of heart development and how congenital heart defects arise when this process goes wrong. This paper was particularly interesting to me as it shows that the same gene can be important in multiple different cell types to carry out distinct functions, and it also displays how crosstalk between different cell types is important during the development of an organ. This work is important to the field of heart development, and other biological fields, as it shows that mutating a gene in one cell type can have detrimental effects on the structure and function of a different cell type. Therefore, it is important to not only investigate the cell type which has been mutated, but to investigate neighbouring cell types which might rely on crosstalk to be able to function correctly.

Questions for authors

  1. Rnf20 is required within both EC to prevent EndMT, but also required within SHF cells, which are known to migrate into the heart tube to assist heart growth1. Do you think Rnf20 is playing a different role in the SHF cells e.g. enabling a more mesenchymal-like state to allow these cells to migrate, or is Rnf20 downregulated in these cells during their migration?
  2. EndMT is required to form the cardiac valves2. Is Rnf20 downregulated in EC undergoing valve formation?

References

  1. Leung, C., Lu, X., Liu, M. & Feng, Q. Rac1 Signaling Is Critical to Cardiomyocyte Polarity and Embryonic Heart Development. J. Am. Heart Assoc. 3, (2014).
  2. Monaghan, M. G. et al. A spatiotemporal observation of EndMT and mesenchymal cell colonization at the onset of human cardiac valve development. Development dev.133843 (2015) doi:10.1242/dev.133843.

 

Tags: development, heart

Posted on: 11 October 2022

doi: https://doi.org/10.1242/prelights.32869

Read preprint (No Ratings Yet)

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the cell biology category:

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:

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

Also in the genetics category:

Semmelweis Symposium 2022: 40th anniversary of international medical education at Semmelweis University

This preList contains preprints discussed during the 'Semmelweis Symposium 2022' (7-9 November), organised around the 40th anniversary of international medical education at Semmelweis University covering a wide range of topics.

 



List by Nándor Lipták

20th “Genetics Workshops in Hungary”, Szeged (25th, September)

In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf

 



List by Nándor Lipták

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

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

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

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
Close