A hydraulic instability drives the cell death decision in the nematode germline

N. T. Chartier, A. Mukherjee, J. Pfanzelter, S. Fürthauer, B. T. Larson, A.W. Fritsch, M. Kreysing, F. Jülicher, S. W. Grill

Posted on: 8 July 2020

Preprint posted on 1 June 2020

Article now published in Nature Physics at

Categories: developmental biology


Oocytes are large and resourceful- they transmit genetic information to the next generation, and provide cellular material to develop a fertilized zygote into an embryo. During oogenesis some germ cells undergo extensive growth, typically at the expense of others that ultimately undergo apoptosis. This phenomenon, and the associated exchange of material is facilitated by a syncytial structure with a shared cytoplasm. Although apoptosis in the germline can serve as quality control by removing damaged cells, the majority of germ cells that undergo apoptosis under normal conditions seem healthy. Chartier et al explore in their work, how from a seemingly homogeneous population, cells are selected to live or die (1).

Figure 1. Volumes and fluxes in the C.elegans gonad. A. Adult hermaphrodite gonad arm. B. Germ cells color-coded according to cell volume. Germ cell volume V along the gonad from distal tip (0% length) to proximal turn (100% length). (From Ref 1.)

Key findings

Transition from a homogeneous to a heterogeneous growth mode.

The authors explore the question on how germ cells are selected to live or die out of a homogeneous population. For this question, they use as a model organism C. elegans. During their maturation, some germ cells grow to become oocytes while others shrink and die by apoptosis. The authors explore a potential relationship between germ cell growth, shrinkage and apoptosis. Following their development by confocal microscopy, they measured individual germ cell volumes, and noted a transition from a homogeneous growth mode, to a heterogeneous one along the gonad. Following this observation, the authors identified the transition zone along 65% of the germline length, and that importantly, proximal to this location physiological apoptosis begins to occur.

Flux of cytoplasm through the rachis along the gonad

The next step consisted on investigating flux of cytoplasm through the rachis along the gonad: An increase in rachis flux implies that germ lines contribute material to the rachis, while a decrease in rachis flux implies that the germ cells receive material from the rachis. Particle imaging velocimetry showed that the flux of cytoplasm through the rachis increases along the distal part of the gonad, peaks at around 60% germline length and decreases thereafter. This suggests germ cells donate material to the rachis prior to 60% germline length, while they receive material from the rachis thereafter. However, germ cells grow prior to 60% germline, despite losing cytoplasm to the rachis, implying they receive material from the outside. Up to 60% gonad length, material uptake is positive and germ cells grow by receiving material from the outside. Material uptake becomes negative beyond 60%, indicating loss of material to the outside.

Pressure differences and transition from homogeneous to heterogeneous mode of germ cell growth

Pressure differences between germ cells and rachis drive cytoplasmic exchange through rachis bridges. The authors thus explored the hydraulics of the gonad. For this, they constructed a one-dimensional physical model that relates pressure profiles to flows of germ cells and rachis cytoplasm, as well as material exchange between germ cells and rachis. Because pressure differences drive cell-to-rachis currents, the pressure difference between cells and rachis turns at the 60% gonad length.

The authors investigated whether the inversion of the pressure difference might explain the transition from homogeneous to heterogeneous mode of germ cell growth. Considering tissue hydraulics, the state of equal germ cell volumes is stable only if the pressure inside germ cells is larger than in the rachis. An instability occurs when the pressure in the rachis is larger than in germ cells: a small difference in germ cell volumes will increase, leading to the growth of the larger germ cell at the expense of the smaller one. The authors conclude this instability is expected to be triggered when the pressure difference between rachis and germ cells becomes negative at 60% gonad length. This hydraulic instability presents a possible mechanism by which germ cells become fated to die.

 An alternative hypothesis: inhibition of apoptosis

The authors explored another hypothesis, whereby unknown molecular signals first induce apoptosis, which subsequently leads to the shrinkage of cells fated to die. For this, they inhibited apoptosis of germ cells by RNAi targeted against caspase ced-3, and evaluated whether the germ cell still shrinks. While in the absence of apoptosis, germ cells are no longer removed, some cells in the proximal region shrink. Moreover, mutant gonads still show a transition from a homogeneous to a heterogeneous mode of growth. This eliminates apoptosis as the cause of germ cell shrinkage and supports the idea that germ cell fate is determined by a hydraulic instability.

Mechanical manipulation of the life and death decision of the gonad

To explore further the idea that the life and death decision of the gonad is a mechanical one, the authors used unidirectional thermoviscous pumping to artificially reduce the volume of individual germ cells to increase their likelihood to undergo apoptosis. This resulted in apoptosis of over 50% of germ cells within 3 hours. Together, this work reveals a robust mechanism of mechanochemical cell fate decision-making in the germline.

What I like about this preprint

I found it an interesting topic, combining in the same question, molecular, cell biology and biophysical aspects. I enjoyed reading the work, and think this opens important questions in the field.

Open questions 

  1. Is the decision to grow or shrink random? Or is it influenced to some extent by location, neighbours, etc?
  2. Until what point of shrinkage is the fate decision reversible?
  3. You explored by molecular methods, influencing apoptosis. How do you link, at a molecular and cell biological level, the initiation of apoptosis with the mechanical aspect?
  4. You used C. elegans as a model organism. To what extent do your findings apply to other organisms?
  5. Out of curiosity, you described material influx from the cytoplasm and the outside. What are the specific components of these materials, and do they also play a role in cell fate?


  1. Chartier NT et al, A hydraulic instability drives the cell death decision in the nematode germline, bioRxiv, 2020



Read preprint (No Ratings Yet)

Have your say

Your email address will not be published. Required fields are marked *

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

Also in the developmental biology category:

Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping

Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, et al.

Selected by 06 June 2024

Bhaval Parmar

Developmental Biology

Lipid-Based Transfection of Zebrafish Embryos: A Robust Protocol for Nucleic Acid Delivery

Aslihan Terzi, Tiger Liao, Adrian Jacobo

Selected by 09 May 2024

Roberto Rodríguez-Morales


Topology changes of the regenerating Hydra define actin nematic defects as mechanical organizers of morphogenesis

Yamini Ravichandran, Matthias Vogg, Karsten Kruse, et al.

Selected by 08 May 2024

Rachel Mckeown

Developmental Biology

preLists 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


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